TGF-β1 and IL-6 expression in rat pineal gland is regulated by norepinephrine and interleukin-1β

Abstract

The pineal gland is part of the neuroendocrine system that modulates immune functions. Because the gland is outside the blood-brain barrier, i t is accessible to direct feedback from circulating cytokines that affect the synthesis and secretion of melatonin. Recent studies have suggested lhat intrinsic immunoregulatory cytokines mediate these neuro-immune interactions under the control of sympathetic innervation to the pineal. This study focused on the expression of transforming growth factor-β1 (TGF-β1) and interleukin-6 (IL-6), two cytokines that have important regulatory functions on both neurons and immune cells. Northern blot RNA analysis showed that TGF-β1, but not IL-6, was expressed in freshly dissected rat pineal glands from neonatal age (l-day-old) into adults. Immunocytochemistry for TGF-β1 in adult glands revealed localization of this protein in astrocytelike cells. The sympathetic neurotransmitter norepinephrine (NE) increased transcript levels for both TGF-β1 and IL-6 in adult pineal organ cultures. The effect of NE on IL-6 expression was not found in dispersed cell cultures established from neonatal pineal glands. The immunoregulatory molecule interleukin-1β (IL-113) up-regulated the expression of both IL-6 and TGF-β1 in adult pineal organ cultures, but not in neonate pineal organ cultures. These findings suggest that TGF-β1 and IL-6 have intrinsic regulatory roles in the pineal gland and that both neural and immune factors are important mechanisms of regulation.