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

Interleukin (IL-) 6 is closely related to gastrointestinal diseases. The qu estion of whether gastric epithelial cell contributes to IL-6 production re mains undefined. We aim to evaluate the regulatory pathway of IL-6 expressi on in gastric epithelial cells, by using different inflammatory cytokines, endotoxin, or protein kinase modulators. IL-6 was measured by ELISA, Phorbo l-12-myristate-13-acetate (PMA), calcium ionophore A23187, TNF-alpha, IL-1 beta, oncostatin M (OSM) but not lipopolysaccharide stimulated IL-6 product ion from gastric epithelial cell, line MKN-28. Blocking protein tyrosine ki nase (PTK) activation by herbimycin A or genistein, or blocking NF-kappa B activation by pyrrolidinedithiocarbamate, reduced the IL-6 expression induc ed by TNF-alpha, IL-1 beta and OSM, Dexamethasone mimicked this effect. Pro tein kinase (PK) C inhibitor only reduced the PMA and OSM induced IL-6 prod uction. 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 inflammat ory cytokines are crucial for IL-6 regulation in gastric epithelial cells, The IL-6 signal pathway is mediated through PTK, NF-kappa B, and also invol ve PKC, intracellular calcium and sensitive to dexamethasone, but is not re lated to PKA, G-protein and IL-10, (C) 2000 Academic Press.