Induction of interleukin-6 release from monocytes by serine proteinases and its potential mechanisms.
Serine proteinases have been recognized playing an important role in inflammation via proteinase-activated receptors (PAR). However, little is known of the influence of serine proteinases and PAR on interleukin-6 (IL-6) secretion from highly purified monocytes. We challenged monocytes from human peripheral blood with serine proteinases and agonist peptides of PAR and measured the levels of IL-6, IL-1beta and IL-12 in culture supernatants by enzyme-linked immunosorbent assay. The results showed that thrombin, trypsin, tryptase and elastase stimulated approximately up to 2.9-, 2.0-, 1.8- and 2.1-fold increase in IL-6 release from monocytes following 16 h of incubation, respectively. Proteinase inhibitors inhibited the actions of proteinases on monocytes. Agonist peptides of PAR-1 (SFLLR-NH(3)) and PAR-4 (GYPGQV-NH(2)), but not PAR-3 (TFRGAP-NH(2)), also induced IL-6 release from monocytes. The proteinases and agonists of PAR failed to stimulate IL-1beta and IL-12 secretion. In conclusion, the induction of IL-6 secretion by serine proteinases may be through the activation of PAR.
Li
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Allergy and Inflammation Research Institute, The Key Immunopharmacology Laboratory of Guangdong Province, Shantou University Medical College, Shantou 515031, Guangdong Province, China.
Wang
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H
He
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D001773:Blood Cells; D002469:Cell Separation; D002478:Cells, Cultured; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007375:Interleukin-1 / Q000378:metabolism; D018664:Interleukin-12 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism*; D019272:Leukocyte Elastase / Q000378:metabolism; D009000:Monocytes / Q000276:immunology*; D044463:Receptor, PAR-1 / Q000819:agonists; D012697:Serine Endopeptidases / Q000378:metabolism*; D015842:Serine Proteinase Inhibitors / Q000494:pharmacology; D013917:Thrombin / Q000378:metabolism; D053802:Tryptases
D007375:Interleukin-1; D015850:Interleukin-6; D044463:Receptor, PAR-1; D015842:Serine Proteinase Inhibitors; D018664:Interleukin-12; D012697:Serine Endopeptidases; D019272:Leukocyte Elastase; D013917:Thrombin; D053802:Tryptases