Regulation of interleukin 6 production in a human gastric epithelial cell line MKN-28.
Interleukin (IL-) 6 is closely related to gastrointestinal diseases. The question of whether gastric epithelial cell contributes to IL-6 production remains undefined. We aim to evaluate the regulatory pathway of IL-6 expression in gastric epithelial cells, by using different inflammatory cytokines, endotoxin, or protein kinase modulators. IL-6 was measured by ELISA. Phorbol-12-myristate-13-acetate (PMA), calcium ionophore A23187, TNF-alpha, IL-1beta, oncostatin M (OSM) but not lipopolysaccharide stimulated IL-6 production from gastric epithelial cell line MKN-28. Blocking protein tyrosine kinase (PTK) activation by herbimycin A or genistein, or blocking NF-kappaB activation by pyrrolidinedithiocarbamate, reduced the IL-6 expression induced by TNF-alpha, IL-1beta and OSM. Dexamethasone mimicked this effect. Protein kinase (PK) C inhibitor only reduced the PMA and OSM induced IL-6 production. Both inhibitors and activators for PKA and G-protein as well as IL-10 had no effects on IL-6 expression. These results indicate that inflammatory cytokines are crucial for IL-6 regulation in gastric epithelial cells. The IL-6 signal pathway is mediated through PTK, NF-kappaB, and also involve PKC, intracellular calcium and sensitive to dexamethasone, but is not related to PKA, G-protein and IL-10.
Ding
S Z
SZ
Department of Medicine, The University of Hong Kong, China.
Cho
C H
CH
Lam
S K
SK
D002470:Cell Survival / Q000187:drug effects; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology; D019204:GTP-Binding Proteins / Q000037:antagonists & inhibitors; D005753:Gastric Mucosa / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology; D016753:Interleukin-10 / Q000235:genetics; D015850:Interleukin-6 / Q000096:biosynthesis*; D007424:Intracellular Fluid / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D016328:NF-kappa B / Q000037:antagonists & inhibitors; D053683:Oncostatin M; D010455:Peptides / Q000494:pharmacology; D011493:Protein Kinase C / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D007375:Interleukin-1; D015850:Interleukin-6; D008070:Lipopolysaccharides; D016328:NF-kappa B; C508351:OSM protein, human; D010455:Peptides; D014409:Tumor Necrosis Factor-alpha; D053683:Oncostatin M; D016753:Interleukin-10; D003907:Dexamethasone; D011505:Protein-Tyrosine Kinases; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C; D019204:GTP-Binding Proteins