DigitalUM :: Browsing by Subject "Cytokines"

Browsing by Subject "Cytokines"

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A novel CD14high CD16high subset of peritoneal macrophages from cirrhotic patients is associated to an increased response to LPS
(Elsevier, 2016-03-01) Martínez-Esparza, M.; Ruiz-Alcaraz, Antonio José; Tapia-Abellán, Ana; Fernández-Fernández, María Dolores; Tristán-Manzano, María; Hernández-Caselles, Trinidad; Sánchez-Velasco, Eduardo; Miras-López, Manuel; García-Penarrubia, Pilar; Bioquímica y Biología Molecular B e Inmunología
The aim of this study was to characterize monocyte-derived macrophages (M-DM) from blood and ascites of cirrhotic patients comparatively with those obtained from blood of healthy controls. The phenotypic profile based on CD14/CD16 expression was analyzed by flow cytometry. Cells were isolated and stimulated in vitro with LPS and heat killed Candida albicans. Phosphorylation of ERK, c-Jun, p38 MAPK, and PKB/Akt was analyzed by Western blotting. A novel CD14(high)CD16(high) M-DM subpopulation is present in ascites (∼33%). The CD14(++)CD16(+) intermediate subset is increased in the blood of cirrhotic patients (∼from 4% to 11%) and is predominant in ascites (49%), while the classical CD14(++)CD16(-) subpopulation is notably reduced in ascites (18%). Basal hyperactivation of ERK and JNK/c-Jun pathways observed in ascites M-DM correlates with CD14/CD16 high expressing subsets, while PI3K/PKB does it with the CD16 low expressing cells. In vitro LPS treatment highly increases ERK1/2, PKB/Akt and c-Jun phosphorylation, while that of p38 MAPK is decreased in M-DM from ascites compared to control blood M-DM. Stimulation of healthy blood M-DM with LPS and C. albicans induced higher phosphorylation levels of p38 than those from ascites. Regarding cytokines secretion, in vitro activated M-DM from ascites of cirrhotic patients produced significantly higher amounts of IL-6, IL-10 and TNF-α, and lower levels of IL-1β and IL-12 than control blood M-DM. In conclusion, a new subpopulation of CD14(high)CD16(high) peritoneal M-DM has been identified in ascites of cirrhotic patients, which is very sensitive to LPS stimulation.
Open Access
Adipose-derived stem cells and adipose-derived stem cell-conditioned medium modulate in situ imbalance between collagen I- and collagen V-mediated IL-17 immune response recovering bleomycin pulmonary fibrosis
(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2020) Gonçalves Felix, Renato; Carvalho Bovolato, Ana Livia; Cotrim, Ondina Silvia; Leão, Patricia dos Santos; Batah, Sabrina Setembre; Golim, Márjorie de Assis; Velosa, Ana Paula P.; Teodoro, Walcy; Martins, Vanessa; Ferreira Cruz, Fernanda; Deffune, Elenice; Fabro, Alexandre Todorovic; Capelozzi, Vera Luiza
The immunogenic collagen V (Col V) and the proinflammatory cytokine interleukin (IL)-17 have been implicated in the pathogenesis of multiple autoimmune diseases. Col V is also up-regulated during adipogenesis and can stimulate adipocyte differentiation in vitro. Conditioned medium (CM) generated from adipose- derived mesenchymal stem cells (MSCs) reduces bleomycin (BLM)-induced lung injury in rats, suggesting a crucial role in situ of immunomodulatory factors secreted by MSCs in these beneficial effects. In the present work, we investigated this hypothesis, analyzing levels of plasma inflammatory mediators and inflammatory and fibrotic mediators in the lung tissue of BLM-injured rats after treatment with MSCs and CM. Pulmonary fibrosis was intratracheally induced by BLM. After 10 days, BLM animals were further randomized into subgroups receiving saline, MSCs, or CM intravenously. On days 14 and 21, the animals were euthanized, and the lungs were examined through protein expression of nitric oxide synthase (NOS), IL-17, transforming growth factor-β (TGF-β), vascular endothelial growth factor, endothelin-1, and the immunogenic Col V through histological quantitative evaluation and plasma levels of fibrinogen, Von Willebrand factor, and platelet-derived growth factor (PDGF). Rats that had been injected with MSCs and CM showed a significant increase in weight and significant improvements at 14 and 21 days after intravenous injection at both time points of analysis of plasma fibrinogen, PDGF, and Von Willebrand factor and NOS-2 expression, supporting an early anti-inflammatory action, thus reducing TGF-β and collagen I fibers. In contrast, intravenous injection of CM was able to significantly increase the deposition of Col V fibers and IL-17 on both day 14 and day 21 as compared with the amount observed in rats from the BLM group and MSC groups. In conclusion, this study reinforces previous observations on the therapeutic properties of MSCs and CM and is the first report to demonstrate the association of its actions with immunomodulatory biomarkers on lung tissue. We concluded that adipose-derived stem cells and adipose- derived stem cells-CM modulate an in situ imbalance between collagen I- and Col V-mediated IL-17 immune response, emerging as a promising therapeutic option for recovering from BLM pulmonary fibrosis
Open Access
Analysis of the anti-inflammatory potential of Brassica bioactive compounds in a human macrophage-like cell model derived from HL-60 cells
(Elsevier, 2022-05) Ruiz Alcaraz, Antonio José; Martínez Sánchez, María Antonia; García Peñarrubia, Pilar; Martínez Esparza, M.; Ramos Molina, Bruno; Moreno, Diego A.; Bioquímica y Biología Molecular B e Inmunología
Background: Chronic inflammatory diseases are major causes of global morbidity and mortality. Acute inflammation is meant to protect the body against foreign agents, but it also plays a major role in tissue repairment. Several mediators are involved in this process, including pro-inflammatory cytokines produced by macrophages. Occasionally, if the inflammatory response is not resolved, the acute inflammatory process can evolve into a chronic inflammation. Natural compounds from vegetables are considered as an important source of active agents with potential to treat or prevent inflammatory related pathologies and could be used as an alternative of the therapeutic agents currently in use, such as non-steroidal anti-inflammatory drugs (NSAIDs), which present several side effects. Methods: In this research work we evaluated in vitro the anti-inflammatory activity of a series of ten phytochemicals present in Brassica, measured as the potential of those compounds to reduce the production of key proinflammatory cytokines (TNF-α, IL-6 and IL-1β) by a human macrophage-like cell model of HL-60 cells Results: Most of the tested phytochemicals (including the most representative bioactive molecules of the major classes of compounds present in cruciferous foods such as glucosinolates, isothiocyanates, hydroxycinnamic acids, flavonols and anthocyanins) demonstrated significant anti-inflammatory activity at micromolar level in the absence of cytotoxic effects in this human macrophage-like cell model. Conclusion: These data confirm that phytochemicals commonly obtained from Brassica may be potential therapeutic leads to treat or prevent human chronic inflammation and related diseases.
Open Access
Changes of inflammatory and oxidative stress biomarkers in dogs with different stages of heart failure
(BioMed Central (BMC), 2020-11-10) Peres Rubio, Camila; Saril, A.; Kocaturk, M.; Tanaka, R.; Koch, J.; Cerón, J.J.; Yilmaz, Z.; Medicina y Cirugía Animal
Background: Heart failure (HF) is associated with changes in inflammatory and oxidative stress biomarkers. This study aimed to evaluate the changes of a panel of inflammatory and oxidative stress biomarkers in dogs with different stages of HF and its relation with the severity of the disease and echocardiographic changes. A total of 29 dogs with HF as a result of myxomatous mitral valve degeneration or dilated cardiomyopathy were included and classified as stage-A (healthy), B (asymptomatic dogs), C (symptomatic dogs) and D (dogs with end-stage HF) according to the ACVIM staging system. In these dogs an ecnhocardiographic examination was performed and cytokines, and inflammatory and oxidative stress markers were evaluated in serum. Results: KC-like was significantly increased in dogs of stage-C (P<0.01) and -D (P < 0.05) compared with stage-A and -B. Stage-D dogs showed significantly higher serum CRP and Hp (P < 0.05) but lower serum antioxidant capacity (PON1, TEAC, CUPRAC, and thiol) compared to stage-A and -B (P < 0.05). After the treatment, serum levels of CRP, Hp and KClike decreased and serum antioxidant levels increased compared to their pre-treatment values. Left ventricular dimension and LA/Ao ratio correlated positively with CRP, MCP-1, and KC-like but negatively with PON1, GM-CSF, IL-7 and antioxidant biomarkers (P < 0.01). Conclusion: Our results showed that dogs with advanced HF show increases in positive acute-phase proteins and selected inflammatory cytokines such as KC-like, and decreases in antioxidant biomarkers, indicating that inflammation and oxidative stress act as collaborative partners in the pathogenesis of HF. Some of these biomarkers of inflammation and oxidative stress could have the potential to be biomarkers to monitor the severity of the disease and the effect of treatment.
Open Access
Chronic atrophic gastritis aggravate chronic periodontitis with Helicobacter pylori infection and CD4+Th cytokines infiltration
(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2020) Luo, Wei; Li, Yaqiang; Luo, Zhenhua; Xu, Baohong
Objective. To investigate the potential effect of chronic atrophic gastritis on chronic periodontitis and further explore the possible mechanism. Methods. Local periodontal lesions were collected from periodontitis tissues of 30 CAG patients and 35 control adults without CAG (non-CAG). Clinical periodontal parameters were recorded, and the expression levels of distinct CD4+ Th specific cytokines at local periodontitis lesions were evaluated by real time PCR (RT-PCR). Helicobacter pylori (H. pylori) detection was carried out in both gastric and periodontitis lesions of CAG and non CAG patients. Results. Clinical parameters analysis showed that the level of clinical attachment loss in periodontitis lesions of CAG group was significantly higher than non-CAG group. It was observed that the infection rate of H. pylori in the CAG group was higher than non-CAG group. Further cytokine analysis showed that Th17 associated cytokines IL-17, IL-21 and IL-23 were increased in periodontal lesions of CAG patients when compared with non-CAG patients. However, Th1, Th2, Th9 and Treg cells specific cytokines were not significantly increased in CAG group when compared with non-CAG group. Conclusions. Patients with CAG demonstrated that significant elevated attachment loss in periodontitis lesions, while elevated Th17 cytokines IL-17, IL-21 and IL-23 participate in immunopathogenesis of both diseases
Open Access
Corticosterone 21-acetate in vivo induces acute stress in chicken thymus: cell proliferation, apoptosis and cytokine responses
(Murcia : F. Hernández, 2004) Franchini, A.; Marchesini, E.; Ottaviani, E.
In vivo effects of acute stress induced by corticosterone 21-acetate in male Gallus domesticus thymus are studied and the steroid actions are evaluated in terms of cell proliferation, apoptosis and cytokine response in 10- and 21-day-old chickens. Steroid treatment induced thymocyte apoptosis and cell death decreased in the cortical-medullar direction and was more evident in younger animals. 24 h after treatment, the observed effect was reversed. The mitotic activity and thymic cells containing cytokine-like molecules were also affected. Indeed, the acute stress stimulated cytokine immunoreactivity to anti-IL-1a, IL-6 and TNF- a antibodies both in epithelial cells and interdigitating cells located in medullar and cortical-medullar regions. The increased cytokine expression observed after 12 h was maintained after 24 h. The comparison between 10- and 21-day-old chickens showed a lower number of cells containing cytokine-like molecules in younger specimens. The present findings suggest that cytokines activated by acute stress in vivo could contribute to restoring immunological homeostasis and influence thymic glucocorticoid-mediated functions.
Open Access
Crescentic glomerulonephritis - a manifestation of a nephritogenic Thl response?
(F. Hernández y Juan F. Madrid. Universidad de Murcia: Departamento de Biología Celular e Histología, 2000) Kitching, A.R.; Holdsworth, S. R.; Tipping, P. G.
Crescentic glomerulonephritis (GN) is the histopathological correlate of the clinical syndrome of rapidly progressive glomerulonephritis. Glomerular crescent formation complicates proliferative forms of GN and indicates severe disease with a poor renal prognosis. In the past 10 years evidence from experimental models of GN and from human disease has accumulated suggesting that crescentic glomerulonephritis is a manifestation of a delayed type hypersensitivity (DTH)-like response to nephritogenic antigens. The elucidation of T helper 1 (Thl) and Th2 subsets in mice and in humans has led to the hypothesis that crescentic GN is a manifestation of a Thl predominant DTH mediated immune response. Recent experiments performed mainly in a murine model of crescentic glomerulonephritis have tested this hypothesis. Crescent formation in this model is substantially interleukin (IL)-12 and interferon-y (IFN-y) dependent. Administration of IL-12, deletion of endogenous IL-4 or IL-lO results in enhanced disease , while administration of exogenous IL-4 and/or IL-IO reduces crescentic injury. These findings, together with the available evidence from human studies (examining the pattern of immune effectors in glomeruli, data on cytokine production by peripheral blood mononuclear cells and case reports of the induction of proliferative and/or crescentic GN by administration of IFN-y or IL2) suggest that human crescentic GN is manifestation of a Thl mediated DTH-like nephritogenic immune response.
Open Access
CXC chemokines and their receptors, A case for a significant biological role in cutaneous wound healing
(Murcia : F. Hernández, 2008) Zaja-Milatovic, Snjezana; Richmond, Ann
Wound healing requires a complex series of reactions and interactions among cells and their mediators, resulting in an overlapping series of events including coagulation, inflammation, epithelialization, formation of granulation tissue, matrix and scar formation. Cytokines and chemokines promote inflammation, angiogenesis, facilitate the passage of leukocytes from circulation into the tissue, and contribute to the regulation of epithelialization. They integrate inflammatory events and reparative processes that are important for modulating wound healing. Thus both cytokines and chemokines are important targets for therapeutic intervention. The chemokine-mediated regulation of angiogenesis is highly sophisticated, fine tuned, and involves proangiogenic chemokines, including CXCL1-3, 5-8 and their receptors, CXCR1 and CXCR2. CXCL1 and CXCR2 are expressed in normal human epidermis and are further induced during the wound healing process of human burn wounds, especially during the inflammatory, epithelialization and angiogenic processes. Human skin explant studies also show CXCR2 is expressed in wounded keratinocytes and Th/1/Th2 cytokine modulation of CXCR2 expression correlates with proliferation of epidermal keratinocytes. Murine excision wound healing, chemical burn wounds and skin organ culture systems are valuable models for examining the role of inflammatory cytokines and chemokines in wound healing.
Open Access
Cytokine profiles in cord blood in relation to prenatal traffic-related air pollution: The NELA cohort
(Wiley, 2022-02) García-Serna, Azahara M.; Martín-Orozco, Elena; Jiménez-Guerrero, Pedro; Hernández-Caselles, Trinidad; Pérez-Fernández, Virginia; Cantero-Cano, Esther; Muñoz-García, María; Molina-Ruano, María Dolores; Rojo-Atenza, Encarna; García-Marcos, Luis; Morales, Eva; Ciencias Sociosanitarias
Background: Outdoor air pollution may disturb immune system development. We investigated whether gestational exposure to traffic-related air pollutants (TRAP) is associated with unstimulated cytokine profiles in newborns. Methods: Data come from 235 newborns of the NELA cohort. Innate response-related cytokines (IL-6, IFN-α, IL1-β, and TNF-α), Th1-related (IFN-γ and IL-2), Th2-related (IL-4, IL-5, and IL-13), Th17-related (IL-17 and IL-23), and immunomodulatory cytokine IL-10 were quantified in the supernatant of unstimulated whole umbilical cord blood cells after 7 days of culture using the Luminex technology. Dispersion/chemical transport modeling was used to estimate long-term (whole pregnancy and trimesters) and short-term (15 days before delivery) residential exposures to traffic-related nitrogen dioxide (NO2 ), particulate matter (PM2.5 and PM10 ), and ozone (O3 ). We fitted multivariable logistic regression, Bayesian kernel machine regression (BKMR), and weighted quantile sum (WQS) regression models. Results: NO2 during the whole pregnancy increased the odds of detection of IL-1β (OR per 10 µg/m3 increase = 1.37; 95% CI, 1.02, 1.85) and IL-6 (OR per 10 µg/m3 increase = 1.32; 95% CI 1.00, 1.75). Increased odds of detected concentrations of IL-10 was found in newborns exposed during whole pregnancy to higher levels of NO2 (OR per 10 µg/m3 increase = 1.30; 95% CI 0.99, 1.69), PM10 (OR per 10 µg/m3 increase = 1.49; 95% CI 0.95, 2.33), and PM2.5 (OR per 5 µg/m3 increase = 1.56; 95% CI 0.97, 2.51). Exposure to O3 during the whole pregnancy increased the odds of detected IL-13 (OR per 10 µg/m3 increase = 1.22; 95% CI 1.01, 1.49). WQS model revealed first and third trimesters of gestation as windows of higher susceptibility. Conclusions: Gestational exposure to TRAP may increase detection of pro-inflammatory, Th2-related, and T regulatory cytokines in newborns. These changes might influence immune system responses later in life.
Embargo
Cytokine profiles in cord blood in relation to prenatal traffic-related air pollution: The NELA cohort
(2022-02-18) García-Serna, Azahara M; Martín-Orozco, Elena; Jiménez-Guerrero, Pedro; Hernández-Caselles, Trinidad; Pérez-Fernández, Virginia; Cantero-Cano, Esther; Muñoz-García, María; Molina-Ruano, María Dolores; Rojo-Atenza, Encarna; García-Marcos, Luis; Morales, Eva; Bioquímica y Biología Molecular B e Inmunología
Background: Outdoor air pollution may disturb immune system development. We investigated whether gestational exposure to traffic-related air pollutants (TRAP) is associated with unstimulated cytokine profiles in newborns. Methods: Data come from 235 newborns of the NELA cohort. Innate response-related cytokines (IL-6, IFN-α, IL1-β, and TNF-α), Th1-related (IFN-γ and IL-2), Th2-related (IL-4, IL-5, and IL-13), Th17-related (IL-17 and IL-23), and immunomodulatory cytokine IL-10 were quantified in the supernatant of unstimulated whole umbilical cord blood cells after 7 days of culture using the Luminex technology. Dispersion/chemical transport modeling was used to estimate long-term (whole pregnancy and trimesters) and short-term (15 days before delivery) residential exposures to traffic-related nitrogen dioxide (NO2 ), particulate matter (PM2.5 and PM10 ), and ozone (O3 ). We fitted multivariable logistic regression, Bayesian kernel machine regression (BKMR), and weighted quantile sum (WQS) regression models. Results: NO2 during the whole pregnancy increased the odds of detection of IL-1β (OR per 10 µg/m3 increase = 1.37; 95% CI, 1.02, 1.85) and IL-6 (OR per 10 µg/m3 increase = 1.32; 95% CI 1.00, 1.75). Increased odds of detected concentrations of IL-10 was found in newborns exposed during whole pregnancy to higher levels of NO2 (OR per 10 µg/m3 increase = 1.30; 95% CI 0.99, 1.69), PM10 (OR per 10 µg/m3 increase = 1.49; 95% CI 0.95, 2.33), and PM2.5 (OR per 5 µg/m3 increase = 1.56; 95% CI 0.97, 2.51). Exposure to O3 during the whole pregnancy increased the odds of detected IL-13 (OR per 10 µg/m3 increase = 1.22; 95% CI 1.01, 1.49). WQS model revealed first and third trimesters of gestation as windows of higher susceptibility. Conclusions: Gestational exposure to TRAP may increase detection of pro-inflammatory, Th2-related, and T regulatory cytokines in newborns. These changes might influence immune system responses later in life.
Open Access
Hyperlipidemia and kidney disease: Concepts derived from histopathology and cell biology of the glomerulus
(F. Hernández y Juan F. Madrid. Universidad de Murcia. Departamento de Biología Celular e Histología, 1998) Kamanna, V. S.; Roh, D. D.; Kirschenbaum, M. A.
The association between hyperlipidemia and renal disease was noted by Virchow as earl y as the 19th ce ntury. Subseq ue ntl y, similar histopatho log ica l lipid depo siti o ns we re confirme d in diverse huma n a nd experimental renal diseases. Altho ugh, no studies have been established in man to suggest a causal re lationship between lipid s and the pathogenesis of rena l disease . compe llin g ev id e nce acc umul a te d in experimental animals suggests a direct role of lipids in the initiation and progression of glome rular disease. These studi es showed that cho lesterol-feed ing to various experimental animals induced the development of glomerul ar injury. Furthermore. the treatment of hype rlipidemic a nima ls with lipid lowering drugs prevented the deve lopment of glomenllosclerosis. In this article, we will rev iew recent advances made in understanding various aspects of lipid-mediated rena l injury inc ludin g bioc he mi ca l mec ha nisms of hype rlipidemia, a possible direct role of hyperlipidemi a in the pa th oge nesis o f ren a l disease, pathobiological acc umulation of lipids and lipoprote ins, biochemi cal and histological similarities between systemic atherosclerosis and glomerulosclerosis, and cellular processes invo lved in the development of glomerul ar disease. Furthermore, we will define cellular and mo lecul ar hypotheses that provide putative mechanisms by which hyperlipidemia a nd a theroge ni c lipo pro tei ns indu ce se ri es o f cy toregulatory peptide- med iated eve nts in vo lved in the development of glomerul ar disease.
Open Access
Immunohistochemical study of macrophage and cytokine dynamics in the gut of scrapie-infected mice
(Murcia : F. Hernández, 2010) Romero-Trevejo, José Lorenzo; Gómez-Villamandos, J. C.; Pedrera, Mirian; Blanco, Alfonso; Bautista, María José; Sánchez-Cordón, Pedro José
To study numerical changes in intestinal macrophages and variations in cytokine production by immune cells in the intestine, conventional C57BL/6J mice were orally infected with the Rocky Mountain Laboratory strain of scrapie. Animals were sacrificed at different timepoints, and samples were taken and processed by routine methods for morphological and immunohistochemical analysis. The results point to a possible role for macrophages in the uptake and transport of the infective agent to Peyer’s patches. The observed increase in macrophage numbers in subepithelial sites, taken in conjunction with a drop in tumour necrosis factor-α production at these sites, suggests a possible secretory inhibition that could be induced by the disease-associated prion protein (PrPd). On the other hand, cytokine dynamics indicated the presence of an impaired Th1-Th2 cell mediated response, which could facilitate the spread of PrPd to the central nervous system. Further research is required to confirm these hypotheses.
Open Access
Immunological and molecular aspects of liver fibrosis in chronic hepatitis C virus infection
(Murcia : F. Hernández, 2005) Giannelli, G.; Antonaci, S.
Chronic C hepatitis represents a major health problem worldwide, mainly because progression of the tissue damage leads to the development of cirrhosis and hepatocellular carcinoma. In this review we discuss the molecular mechanisms underlying the development of liver fibrosis. In particular we consider some immunologic aspects that regulate the interaction between HCV and the host immune defense. Reflections are made about the roles played by the host capacity to respond to the viral infection during therapy and the consequences of the deposition of extracellular matrix (ECM) proteins leading to the development of fibrosis. The involvement of inflammatory cytokines in regulating the proteolytic remodeling of the liver and the ECM turn-over is essential for the activation of hepatic stellate cells (HSCs), that have an important role in the progression of liver fibrosis. Finally, we analyze one of the aspects involved in the activation of the HSCs, namely the proteolytic remodeling of the surrounding environment.
Open Access
In situ detection and distribution of inflammatory cytokines during the course of infection with Nocardia brasiliensis
(Murcia : F. Hernández, 2008) Solis-Soto, J.M.; Quintanilla-Rodriguez, L.E.; Meester, I.; Segoviano-Ramirez, J.C.; Vazquez-Juarez, J.L.; Salinas Carmona, M.C.
Actinomycetoma, caused by the intracellular bacterium Nocardia brasiliensis, is characterized by an infiltration of several inflammatory cell populations. To explore aspects of the immune response in the pathogenesis of these bacteria we injected 106 CFU in footpads of BALB/c mice. After 1, 2, 3, 4, 7, 30 and 90 days immunohistochemistry was performed to compare presence and distribution of the inflammatory cytokines TNF-alpha, IL-1 beta, IL-6, IFN-gamma, IL-4, IL-10, and TGF-beta. Analysis of serial paraffin tissue sections showed strong participation and differences in distribution of cytokine-producing cells during the course of infection. Several TNF-alpha immunoreactive lymphocytes of the dermis were present during the course of the infection, but absent in the site of inflammation. During the first 4 days, IL-1 beta immunoreactivity was observed in dendritic epidermal cells and in cells surrounding the neutrophils around the grain. In later stages of infection, immunoreactive cells to this cytokine were mainly in the periphery of the microabscesses. Strong immunoreactivity was observed with IL-6 during the course of infection. Some cells in the epidermis and dermis, as well as muscle cells and several cells at the periphery of the microabscesses, showed strong IL-6 immunoreactivity. Cells immunoreactive to IL-4, IL-10, IFN-gamma and TGFbeta were present at the site of infection and, in later stages, in cells at the periphery of the microabscesses. In conclusion a mix of proinflammatory and antiinflammatory cytokines are produced at the same time by host cells. According to their distribution, inflammatory cytokines seems to have different functions during the course of infection with the intracellular bacterium N. brasiliensis.
Open Access
Inflammatory cytokine and chemokine expression in sympathetic ophthalmia: a pilot study
(F. Hernández y J.F. Madrid. Murcia: Universidad de Murcia, Departamento de Biología Celular e Histología., 2011) Furusato, Emiko; Shen, DeFen; Cao, Xiaoguang; Furusato, Bungo; Nussenblat, Robert B.; Rushing, Elisabeth J.; Chan, Chi-Chao
Sympathetic ophthalmia is a bilateral uveitis that develops after penetrating injury to one eye. This study aimed to identify the inflammatory cellular sub-phenotypes and expression of pertinent inflammatory cytokines/chemokines in sympathetic ophthalmia (SO). Dalen-Fuchs nodules (DFN), granulomas, and non-granulomatous foci of inflammation were micro-dissected from 15 cases. RNA was extracted, and quantitative PCR was performed to measure IL-17, IL-18, IL-23, IFN-γ, CCL19, CXCL11, CCL17, and CCL22 transcripts. Immunohistochemical methods were used to characterize CD3, CD4, CD8, CD20, CD68, and CD163 expression. Non-granulomatous lymphocytes were predominantly CD3-positive and expressed more IFN-γ than cells within granulomas, consistent with Th1 cells. In contrast, granulomas and DFN contained mainly CD68+, CD163+/- and expressed more IL-17, IL-18, IL-23, CCL19, and CXCL11 than non-granulomatous cells. Our data indicate for the first time that M1 macrophages are the predominant inflammatory cells within granulomas and DFN of SO. We further observed high levels of IL-17 within granulomas and the presence of Th1 and M1 cells.
Open Access
Inflammatory status in human hepatic cirrhosis
(Baishideng publishing Group, 2015-11-07) Martínez-Esparza, M.; Tristán-Manzano, María; Ruiz-Alcaraz, Antonio José; García-Peñarrubia, Pilar; Bioquímica y Biología Molecular B e Inmunología
This review focuses on new findings about the inflammatory status involved in the development of human liver cirrhosis induced by the two main causes, hepatitis C virus (HCV) infection and chronic alcohol abuse, avoiding results obtained from animal models. When liver is faced to a persistent and/or intense local damage the maintained inflammatory response gives rise to a progressive replacement of normal hepatic tissue by non-functional fibrotic scar. The imbalance between tissue regeneration and fibrosis will determine the outcome toward health recovery or hepatic cirrhosis. In all cases progression toward liver cirrhosis is caused by a dysregulation of mechanisms that govern the balance between activation/homeostasis of the immune system. Detecting differences between the inflammatory status in HCV-induced vs alcohol-induced cirrhosis could be useful to identify specific targets for preventive and therapeutic intervention in each case. Thus, although survival of patients with alcoholic cirrhosis seems to be similar to that of patients with HCV-related cirrhosis (HCV-C), there are important differences in the altered cellular and molecular mechanisms implicated in the progression toward human liver cirrhosis. The predominant features of HCV-C are more related with those that allow viral evasion of the immune defenses, especially although not exclusively, inhibition of interferons secretion, natural killer cells activation and T cell-mediated cytotoxicity. On the contrary, the inflammatory status of alcohol-induced cirrhosis is determined by the combined effect of direct hepatotoxicity of ethanol metabolites and increases of the intestinal permeability, allowing bacteria and bacterial products translocation, into the portal circulation, mesenteric lymph nodes and peritoneal cavity. This phenomenon generates a stronger pro-inflammatory response compared with HCV-related cirrhosis. Hence, therapeutic intervention in HCV-related cirrhosis must be mainly focused to counteract HCV-immune system evasion, while in the case of alcohol-induced cirrhosis it must try to break the inflammatory loop established at the gut-mesenteric lymph nodes-peritoneal-systemic axis.
Open Access
Intrauterine Infusion of TGF-β1 Prior to Insemination, Alike Seminal Plasma, Influences Endometrial Cytokine Responses but Does Not Impact the Timing of the Progression of Pre-Implantation Pig Embryo Development
(MDPI, 2021-02-17) Martínez, Cristina A.; Cambra, Josep M.; Lucas, Xiomara; Ferreira-Dias, Graça; Rodríguez-Martínez, Heriberto; Gil, María A.; Martínez, Emilio A.; Cuello, Cristina; Parrilla, Inmaculada; Medicina y Cirugía Animal
Seminal plasma (SP) in the female genital tract induces changes that affect multiple reproductive processes. One of the active components in SP is the transforming growth factor β1 (TGF-β1), which has major roles in embryo development and pregnancy. Embryo transfer (ET) technology is welcomed by the pig industry provided that embryo quality at embryo collection as well as the fertility and prolificacy of the recipients after the ET is increased. This study evaluated different intrauterine infusion treatments at estrus (40 mL of SP, TGF-β1 cytokine in the extender, or the extender alone (control)) by mimicking an ET scenario in so-called "donor" (inseminated) and "recipient" (uninseminated) sows. On day 6 (day 0-onset of estrus), all "donors" were laparotomized to determine their pregnancy status (presence and developmental stage of the embryos). In addition, endometrial explants were collected from pregnant "donors" and cyclic "recipients," incubated for 24 h, and analyzed for cytokine production. SP infusions (unlike TGF-β1 infusions) positively influenced the developmental stage of day 6 embryos. Infusion treatments differentially influenced the endometrial cytokine production, mainly in donors. We concluded that SP infusions prior to AI not only impacted the porcine preimplantation embryo development but also influenced the endometrial cytokine production six days after treatment, both in donors and recipients.
Open Access
Isolation of functional mature peritoneal macrophages from healthy humans.
(Wiley, 2019-11-06) Ruiz Alcaraz, Antonio José; Martínez Banaclocha, Helios; Marín Sánchez, Pilar; Carmona Martínez, Violeta; Iniesta Albadalejo, Miguel Ángel; Tristán Manzano, María; Tapia Abellán, Ana; García Peñarrubia, Pilar; Machado Linde, Francisco; Pelegrín, Pablo; Martínez Esparza, M.; Bioquímica y Biología Molecular B e Inmunología
Macrophages play an important role in the inflammatory response. Their various biological functions are induced by different membrane receptors, including Toll-like receptors, which trigger several intracellular signaling cascades and activate the inflammasomes, which in turn elicit the release of inflammatory mediators such as cytokines. In this study, we present a novel method for the isolation of human mature peritoneal macrophages. This method can be easily implemented by gynecologists who routinely perform laparoscopy for sterilization by tubal ligation or surgically intervene in benign gynecological pathologies. Our method confirms that macrophages are the main peritoneal leukocyte subpopulation isolated from the human peritoneum in homeostasis. We showed that primary human peritoneal macrophages present phagocytic and oxidative activities, and respond to activation of the main proinflammatory pathways such as Toll-like receptors and inflammasomes, resulting in the secretion of different proinflammatory cytokines. Therefore, this method provides a useful tool for characterizing primary human macrophages as control cells for studies of molecular inflammatory pathways in steady-state conditions and for comparing them with those obtained from pathologies involving the peritoneal cavity. Furthermore, it will facilitate advances in the screening of anti-inflammatory compounds in the human system.
Open Access
lnterferons and cell growth control
(Murcia : F. Hernández, 2000) Kalvakolanu, D.V.
Cytokines modulate cell growth, differentiation, and immune defenses in the vertebrates. Interferons (IFNs) are a unique class of cytokines that stimulate antiviral, antitumor and antigen presentation by inducing the expression of several cellular genes. Recent studies have identified a novel gene regulatory pathway activated by IFNs, which serves as a paradigm for most cytokine signal transduction pathways. A number of genes induced by IFNs participate in cell growth regulation and apoptosis. These include novel tumor suppressor genes. Although discovered as IFN-regulated factors, deletions of these genes cause leukemias in experimental models and in human patients. Genetic approaches have identified several novel regulators of apoptosis. Studies on the mechanism of action of these growth regulatory molecules are not only useful in identifying novel targets for the development of therapeutics but also help understand the molecular basis for loss of cell growth control and resistance to IFNs. This review focuses on the functions and roles of IFN regulated factors in cell growth control and mechanisms of disruption of IFN action in cancer cells.
Open Access
Measurable cytokine concentrations in pig seminal plasma are modified by semen handling and storage
(MDPI, 2020-09-07) Padilla, Lorena; Barranco, Isabel; Parrilla, Inmaculada; Lucas, Xiomara; Rodríguez-Martínez, Heriberto; Roca, Jordi; Medicina y Cirugía Animal
Sample handling and storing are critical steps for the reliable measurement of circulating biomolecules in biological fluids. This study evaluates how cytokine measurements in pig seminal plasma (SP) vary depending on semen handling and SP storage. Thirteen cytokines (GM-CSF, IFNγ, IL-1α, IL-1β, IL-1ra, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12, IL-18 and TNFα) were measured using Luminex xMAP® technology in individual seminal plasma (SP) samples (n = 62) from healthy breeding boars. Three separate experiments explored the delay (2 h and 24 h) in SP collection after ejaculation (Experiment 1) and SP storage, either short-term (5 °C, -20 °C and -80 °C for 72 h, Experiment 2) or long-term (at -20 °C and -80 °C for two months, Experiment 3), before analysis. Levels in fresh SP-samples were used as baseline control values. Delays in SP harvesting of up to 24 h did not substantially impact SP cytokine measurements. Some cytokines showed instability in stored SP samples, mainly in long-term storage. Ideally, cytokines in pig SP should be measured in fresh samples harvested within 24 h after ejaculation. If storage of SP is imperative, storage conditions should be adjusted for each cytokine.