Lipopolysaccharide directly stimulates the intrapituitary interleukin-6 production by folliculostellate cells via specific receptors and the p38alpha mitogen-activated protein kinase/nuclear factor-kappaB pathway.
Bacterial lipopolysaccharide (LPS) activates the immune system and induces increases in peripheral cytokines, which, in turn, affect the endocrine system. In particular, LPS-induced cytokines stimulate the hypothalamic-pituitary-adrenal axis to increase levels of antiinflammatory-acting glucocorticoids. In the present work, we show that LPS directly stimulates interleukin (IL)-6 release by mouse pituitary folliculostellate (FS) TtT/GF tumor cells and FS cells of mouse pituitary cell cultures. The stimulatory effect of LPS was strongly enhanced in the presence of serum, suggesting that LPS is only fully active as a complex with LPS-binding protein (LBP). Both TtT/GF cells and mouse pituitaries expressed CD14, which binds the LPS/LBP complex, and Toll-like receptor type 4, which induces LPS signals. LPS increased phospoinositol turnover in TtT/GF cells and induced phosphorylation of p38alpha mitogen-activated protein kinase and the inhibitor (IkappaB) of nuclear factor-kappa B. Nuclear factor-kappa B was activated by LPS in TtT/GF cells. Functional studies demonstrated that My4 (an antibody blocking the interaction between LPS/LBP and CD14), SB203580, (a specific inhibitor of p38alpha mitogen-activated protein kinase phosphorylation), dexamethasone, and the messenger RNA translation inhibitor cycloheximide all inhibited LPS-induced IL-6 production by TtT/GF cells and mouse pituitary FS cells. LPS-induced intrapituitary IL-6 may modulate the function of anterior pituitary cells during bacterial infection/inflammation.
Lohrer
P
P
Max Planck Institute of Psychiatry, Department of Endocrinology, Munich, Germany.
Gloddek
J
J
Nagashima
A C
AC
Korali
Z
Z
Hopfner
U
U
Pereda
M P
MP
Arzt
E
E
Stalla
G K
GK
Renner
U
U
D000209:Acute-Phase Proteins; D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D002352:Carrier Proteins / Q000378:metabolism / Q000494:pharmacology; D002460:Cell Line; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism; D003513:Cycloheximide / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology; D005938:Glucocorticoids / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology; D007295:Inositol Phosphates / Q000378:metabolism; D015850:Interleukin-6 / Q000096:biosynthesis*; D018950:Lipopolysaccharide Receptors / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008297:Male; D008562:Membrane Glycoproteins; D051379:Mice; D008810:Mice, Inbred C57BL; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism*; D010716:Phosphatidylinositols / Q000378:metabolism; D010766:Phosphorylation; D010903:Pituitary Gland, Anterior / Q000378:metabolism*; D011725:Pyridines / Q000494:pharmacology; D015398:Signal Transduction; D000099231:Lipopolysaccharide-Binding Protein
D000209:Acute-Phase Proteins; D000906:Antibodies; D002352:Carrier Proteins; D000242:Cyclic AMP; D003513:Cycloheximide; D003907:Dexamethasone; D005938:Glucocorticoids; D007093:Imidazoles; D007295:Inositol Phosphates; D015850:Interleukin-6; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D020928:Mitogen-Activated Protein Kinases; D016328:NF-kappa B; D010716:Phosphatidylinositols; D011725:Pyridines; D000099231:Lipopolysaccharide-Binding Protein; C002647:inositol 1-phosphate; C093642:SB 203580