Interleukin-1 β Modulates Melatonin Secretion in Ovine Pineal Gland: Ex Vivo Study.

A P Herman,D Tomaszewska-Zaremba,K Król,A Krawczyńska,H Antushevich,J Bochenek,B Pawlina,J Skipor,E Marciniak

doi:10.1155/2015/526464

Abstract

The study was designed to determine the effect of proinflammatory cytokine, interleukin- (IL-) 1β, on melatonin release and expression enzymes essential for this hormone synthesis: arylalkylamine-N-acetyltransferase (AA-NAT) and hydroxyindole-O-methyltransferase (HIOMT) in ovine pineal gland, taking into account the immune status of animals before sacrificing. Ewes were injected by lipopolysaccharide (LPS; 400 ng/kg) or saline, two hours after sunset during short day period (December). Animals were euthanized three hours after the injection. Next, the pineal glands were collected and divided into four explants. The explants were incubated with (1) medium 199 (control explants), (2) norepinephrine (NE; 10 µM), (3) IL-1β (75 pg/mL), or (4) NE + IL-1β. It was found that IL-1β abolished (P < 0.05) NE-induced increase in melatonin release. Treatment with IL-1β also reduced (P < 0.05) expression of AA-NAT enzyme compared to NE-treated explants. There was no effect of NE or IL-1β treatment on gene expression of HIOMT; however, the pineal fragments isolated from LPS-treated animals were characterized by elevated (P < 0.05) expression of HIOMT mRNA and protein compared to the explants from saline-treated ewes. Our study proves that IL-1β suppresses melatonin secretion and its action seems to be targeted on the reduction of pineal AA-NAT protein expression.

Highlights

The daily changes in environmental light conditions have profound impact on all aspects of vertebrate physiology
The results of our study demonstrate that IL-1β may be an important mediator via immune system which regulates the melatonin secretion
Our ex vivo study showed that IL-1β-induced decrease in melatonin release generally reflects the changes occurring in AA-NAT protein expression, because the effect of IL1β on the transcription of this enzyme seems to be more ambiguous

Summary

Introduction

The daily changes in environmental light conditions have profound impact on all aspects of vertebrate physiology. Paracrine, and autocrine effects in the leukocyte compartment and differentially modulates proinflammatory enzymes, controls production of inflammatory mediators such as cytokines and leukotrienes, and regulates the lifespan of leukocytes by interfering with apoptotic processes. It was described that the systemic inflammation induced by the injection of LPS stimulated the gene expression of potent and pleiotropic proinflammatory cytokine, interleukin- (IL-) 1β, directly in the rat pineal gland [22], which suggests that this cytokine may be involved in the inflammatory-dependent modulation of melatonin secretion. The current study was designed to determine the effect of IL-1β on melatonin release and expression of AA-NAT and HIOMT in ovine pineal gland, taking into account the immune status of animals before sacrificing, because our previous study carried out on the pituitary explants showed that immune status of organ donor may affect the responsiveness of the gland on this cytokine action [23]

Materials and Methods

Assays

Results

Discussion