Regulation of interleukin 6 production in a human gastric epithelial cell line MKN-28.

Abstract

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.

• Authors: S Z Ding, C H Cho, S K Lam
• Journal: Cytokine (Cytokine) Vol. 12 Issue 7 Pg. 1129-35 (Jul 2000) ISSN: 1043-4666 [Print] England
• PMID: 10880263 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright 2000 Academic Press.

Chemical References

• Interleukin-1
• Interleukin-6
• Lipopolysaccharides
• NF-kappa B
• OSM protein, human
• Peptides
• Tumor Necrosis Factor-alpha
• Oncostatin M
• Interleukin-10
• Dexamethasone
• Protein-Tyrosine Kinases
• Cyclic AMP-Dependent Protein Kinases
• Protein Kinase C
• GTP-Binding Proteins

Topics

• Cell Survival (drug effects)
• Cyclic AMP-Dependent Protein Kinases (antagonists & inhibitors, metabolism)
• Dexamethasone (pharmacology)
• GTP-Binding Proteins (antagonists & inhibitors)
• Gastric Mucosa (immunology, metabolism)
• Humans
• Interleukin-1 (pharmacology)
• Interleukin-10 (genetics)
• Interleukin-6 (biosynthesis)
• Intracellular Fluid (metabolism)
• Lipopolysaccharides (pharmacology)
• NF-kappa B (antagonists & inhibitors)
• Oncostatin M
• Peptides (pharmacology)
• Protein Kinase C (metabolism)
• Protein-Tyrosine Kinases (antagonists & inhibitors)
• Tumor Cells, Cultured
• Tumor Necrosis Factor-alpha (pharmacology)