TGF-ß1 and IL-6 expression in rat pineal gland is regulated by norepinephrine and interleukin-1 ß

Abstract

T he pineal g land is part of th e neur oendoc rin e system that modulat es immun e functions. Beca use the gland is outside the blood-brain barrier, il is accessibl e to dir ec t feedback from circul atin g cyto kin es that affec t th e sy nth esis and secreti on of melatonin . Recent studi es have suggested that intrinsic immunoregul atory cytokines med iate these neuro-immune int e ra cti o ns und er th e co ntr o l of sympathetic innervation to the pineal. This study focused on th e expression of transfo rmin g growt h factor-f3 1 (TGF-f3I) and interl eukin-6 (IL-6), two cy toki nes th at have important regula tory functions on both neurons and immune cells. Northern blot RNA analysis showed that TGF-f3l, but not IL-6, was expressed in freshly dissected rat pineal glands from neo natal age (l -day-o ld) into ad ults. Immun ocy toc hemistry for TGF-B1 in adult glands revealed localization of this protein in astrocy telik e cells. The sy mp ath e tic ne ur o tr ansmitt e r norepinephrine (NE) increased transcript levels for both TGF-f31 and IL-6 in adu lt pinea l organ cultures. The effect of NE o n I L-6 exp ressio n was not found in dispersed cell cultures established from neonatal pineal glands. The immunoregul atory molecule interleukin-l/3 (IL-l /3) up-regulat ed th e expression of both IL-6 and TGF-/31 in ad ult pineal organ cultures, but not in neonate pineal organ cultures. These findings suggest that TGF- /31 and IL-6 have intrinsic regul atory roles in the pinea l gland and that both neural and immune factors are important mechanisms of regulation.