ABSTRACT
OBJECTIVES: Stimulation of cell results in a variety of early biochemical events, known as signal transduction pathway and ultimately leads to final outcome like cell proliferation or cytokine production. The intracellular signal transduction pathway of IL-6 production by LPS stimulated fibroblast is not well defined. In present study, we investigated what signal transduction pathway is involved in IL-6 production. METHODS: We examined the effects of various inhi bitors of signal transduction pathway including pertussis toxin, cholera toxin, genistein, indomethacin, EDTA, nife dpine, sphingosine, staurosporine, and H8 on the produc tion of IL-6 by human fetal fibroblast MRC-5 after stimulation with LPS. IL-6 was measured by bioassay in supernatant of LPS stimulated fibroblast MRC-5 after pretreatment with inhibitors. RESULTS: Calcium inhibitor (EDTA) and protein kinase inhibitor (staurosporine) reduced IL-6 production by LPS stimulated fibroblast. Protein tyrosine kinase inhibitor(Genistein) and PKC inhibitor(sphingosine) had no influence on IL-6 production. Cholera toxin and pro staglandin inhibitor (indomethacin) led to increase in IL-6 production by LPS stimulated fibroblasts. CONCLUSION:: These results suggest that G protein associated receptors, through the calcium dependent pathway, are working in IL-6 production by LPS stim ulated fibroblasts.