Korean J Med.  1998 Mar;54(3):415-422.

Intracellular signal transduction of interleukin-6 production bylipopolysaccharide-stimulated fibroblasts

• Joo JH
• Ki SY
• Moon SH
• Jung SH
• Kim HT
• Uh ST
• Kim YH
• Park CS

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.

Keyword

Interleukin-6; Lipopolysaccharide; Fibroblast; Intracellular signal transduction

MeSH Terms

Biological Assay
Calcium
Cell Proliferation
Cholera Toxin
Edetic Acid
Fibroblasts*
Genistein
GTP-Binding Proteins
Humans
Indomethacin
Interleukin-6*
Pertussis Toxin
Protein Kinases
Protein-Tyrosine Kinases
Signal Transduction*
Sphingosine
Staurosporine
Calcium
Cholera Toxin
Edetic Acid
GTP-Binding Proteins
Genistein
Indomethacin
Interleukin-6
Pertussis Toxin
Protein Kinases
Protein-Tyrosine Kinases
Sphingosine
Staurosporine