Production of interleukin-6 by anterior pituitary cells is stimulated by increased intracellular adenosine 3',5'-monophosphate and vasoactive intestinal peptide.
Interleukin-6 (IL-6) is an inflammatory cytokine that is produced by a variety of cells and tissues. We recently demonstrated that IL-6 is produced by anterior pituitary cells in response to the bacterial endotoxin lipopolysaccharide and phorbol diester in vitro. Lipopolysaccharide (0.01-100 ng/ml) increased, whereas dexamethasone (0.1-100 nM) decreased, IL-6 production by anterior pituitary cells in vitro as measured by the 7TD1 cell growth factor assay. In addition, we now report that IL-6 production by anterior pituitary cells is stimulated by agents that elevate intracellular cAMP concentrations. Exposure of anterior pituitary cells to (Bu)2cAMP (0.01-10 mM), prostaglandin E2 (1.0-1000 nM), forskolin (50-1000 nM), or cholera toxin (0.25-250 ng/ml) for 6 h resulted in concentration-related increases in the production of IL-6, which, in the cases of forskolin and cholera toxin, correlated well with increased intracellular cAMP concentrations. Vasoactive intestinal peptide (1-1000 nM), which stimulates adenylate cyclase activity in the anterior pituitary, caused a concentration-related enhancement of IL-6 production that was unaffected in the presence of 10-100 nM somatostatin. In contrast, GH-releasing factor had no effect on IL-6 production. These data suggest that anterior pituitary cells produce IL-6 in response to increased intracellular cAMP, and that the neuropeptide vasoactive intestinal peptide may act to regulate IL-6 production.
Spangelo
B L
BL
Department of Medicine, University of Virginia Health Sciences Center, Charlottesville 22908.
Isakson
P C
PC
MacLeod
R M
RM
D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D002772:Cholera Toxin / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology; D003346:Corticotropin-Releasing Hormone / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism*; D003907:Dexamethasone / Q000494:pharmacology; D005260:Female; D013007:Growth Hormone-Releasing Hormone / Q000494:pharmacology; D015850:Interleukin-6 / Q000096:biosynthesis*; D008070:Lipopolysaccharides / Q000494:pharmacology; D010903:Pituitary Gland, Anterior / Q000187:drug effects / Q000378:metabolism*; D011458:Prostaglandins E / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012485:Salmonella typhi; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology*
D015850:Interleukin-6; D008070:Lipopolysaccharides; D011458:Prostaglandins E; D005576:Colforsin; D014660:Vasoactive Intestinal Peptide; D003994:Bucladesine; D003907:Dexamethasone; D002772:Cholera Toxin; D003346:Corticotropin-Releasing Hormone; D013007:Growth Hormone-Releasing Hormone; D000242:Cyclic AMP