Thrombin induces IL-6 production in fibroblasts and epithelial cells. Evidence for the involvement of the seven-transmembrane domain (STD) receptor for alpha-thrombin.
alpha-Thrombin is a multifunctional serine protease that has an important role in the coagulation cascade, wound healing, and inflammatory response. In this study, we show that thrombin induces IL-6 production in human epithelial cells and fibroblasts. ELISA and Northern blot analyses showed that physiologic concentrations of thrombin (0.1-1 micrograms/ml) induced IL-6 production in human lung fibroblasts, skin fibroblasts, and epithelial cells. Hirudin, a thrombin inhibitor, completely blocked IL-6 induction by thrombin. Treatment of fibroblasts with inactivated diisopropylphosphofluoridate (DIP)-alpha-thrombin, gamma-thrombin, or trypsin had no effect on IL-6 production. In contrast, treatment with the thrombin-tethered ligand receptor peptide TRP-7 (SFLLRNP) induced IL-6 production, but at lower levels than that induced by native alpha-thrombin. Finally, IL-6 pretreatment of lung or skin fibroblasts resulted in the enhanced production of IL-6 following exposure to thrombin. These results suggest that fibroblasts and epithelial cells may represent a significant source of IL-6 in the inflammatory response to tissue injury, and that cytokine production is an important biologic consequence of thrombin's interaction with its seven-transmembrane domain (STD) receptor.
Sower
L E
LE
Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston 77555, USA.
Froelich
C J
CJ
Carney
D H
DH
Fenton
J W
JW
Klimpel
G R
GR
D000595:Amino Acid Sequence; D002460:Cell Line; D004847:Epithelial Cells; D004848:Epithelium / Q000378:metabolism*; D005347:Fibroblasts / Q000378:metabolism*; D006801:Humans; D015850:Interleukin-6 / Q000096:biosynthesis* / Q000502:physiology; D008969:Molecular Sequence Data; D018179:Receptors, Thrombin / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000502:physiology*; D013917:Thrombin / Q000502:physiology*
D015850:Interleukin-6; D018179:Receptors, Thrombin; D013917:Thrombin