Central Interleukin-1ß Suppresses the Nocturnal Secretion of Melatonin.

In vertebrates, numerous processes occur in a rhythmic manner. The hormonal signal reliably reflecting the environmental light conditions is melatonin. Nocturnal melatonin secretion patterns could be disturbed in pathophysiological states, including inflammation, Alzheimer's disease, and depression. All of these states share common elements in their aetiology, including the overexpression of interleukin- (IL-) 1ß in the central nervous system. Therefore, the present study was designed to determine the effect of the central injection of exogenous IL-1ß on melatonin release and on the expression of the enzymes of the melatonin biosynthetic pathway in the pineal gland of ewe. It was found that intracerebroventricular injections of IL-1ß (50 µg/animal) suppressed (P < 0.05) nocturnal melatonin secretion in sheep regardless of the photoperiod. This may have resulted from decreased (P < 0.05) synthesis of the melatonin intermediate serotonin, which may have resulted, at least partially, from a reduced expression of tryptophan hydroxylase. IL-1ß also inhibited (P < 0.05) the expression of the melatonin rhythm enzyme arylalkylamine-N-acetyltransferase and hydroxyindole-O-methyltransferase. However, the ability of IL-1ß to affect the expression of these enzymes was dependent upon the photoperiod. Our study may shed new light on the role of central IL-1ß in the aetiology of disruptions in melatonin secretion.

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

The study was designed to determine the effect of proinflammatory cytokine, interleukin- (IL-) 1ß, 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-1ß (75 pg/mL), or (4) NE + IL-1ß. It was found that IL-1ß abolished (P < 0.05) NE-induced increase in melatonin release. Treatment with IL-1ß also reduced (P < 0.05) expression of AA-NAT enzyme compared to NE-treated explants. There was no effect of NE or IL-1ß 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-1ß suppresses melatonin secretion and its action seems to be targeted on the reduction of pineal AA-NAT protein expression.

Influence of fundectomy and intraperitoneal or intragastric administration of apelin on apoptosis, mitosis, and DNA repair enzyme OGG1,2 expression in adult rats gastrointestinal tract and pancreas.

Apelin, endogenous ligand of G protein-coupled apelin receptor (APJ), is released into the gastrointestinal lumen, however, local effect of luminal apelin on gut epithelium has not been elucidated so far. The present study aimed to determine the effects of fundectomy, and intraperitoneal or intragastric administration of apelin on pancreatic, gastric and intestinal epithelium apoptosis, mitosis and DNA repair enzyme OGG1,2 expression in adult Wistar rats. Apelin-13 was given by intraperitoneal or gastric gavage twice a day for 10 days (100 nmol/kg b. wt./day). Fundectomized rats did not receive apelin. Control groups received saline as placebo. At the end of the experiment the rats were sacrificed and the pancreas, gastric fundus, duodenum, middle jejunum and colon tissue samples were harvested for immunofluorescence studies. Intraperitoneal and intragastric apelin-13 reduced apoptosis, mitosis and number of DNA damages in rats gastrointestinal tract (p≤0.001) as compared to control. In fundectomized rats, the apoptotic index in the pancreas and colon was decreased (p<0.001), and in the stomach and jejunum was increased (p<0.001). Mitotic index was decreased in all gastrointestinal tissues. Number of DNA damages (p≤0.001) in fundectomized rats was reduced except stomach where OGG1,2 expression was increased (p≤0.001) as compared to control. In conclusion, circulating and luminal exogenous apelin-13 caused similar effects on intestinal epithelium. Endogenous (gastric) apelin is important for renewal of intestinal epithelium in adult rats. Pharmacological doses of apelin-13 may reduce the cell turnover in the upper gastrointestinal tract epithelium and pancreas, and improve the overall gut health.