Induction of IL-6 release from human T cells by PAR-1 and PAR-2 agonists.
Proteinase-activated receptors (PAR) have been recognized as playing an important role in inflammation and immune response. However, little is known of the expression and function of PAR on human T cells. In this study, the expression of PAR on highly purified human T cells was determined and the secretion of IL-6 from cultured T cells in response to serine proteinases and agonist peptides of PAR was examined. The results showed that T cells express PAR-1, PAR-2 and PAR-3 proteins and genes. Thrombin, trypsin and tryptase, but not elastase, were able to stimulate concentration-dependent secretion of IL-6 from T cells following a 16 h incubation period. The specific inhibitors of thrombin, trypsin and tryptase inhibited the actions of these proteinases on T cells, indicating that the enzymatic activity is essential for their actions. Agonist peptides of PAR SFLLR-NH2, TFLLRN-NH2 and SLIGKV-NH2, but not TFRGAP-NH2, GYPGQV-NH2 and AYPGKF-NH2, are also capable of inducing IL-6 release from T cells. In conclusion, induction of IL-6 secretion from T cells by thrombin, trypsin and tryptase is probably through the activation of PAR, suggesting that serine proteinases are involved in the regulation of immune response of the body.
Li
Tao
T
Allergy and Inflammation Research Institute, The Key Immunopharmacology Laboratory of Guangdong Province, Shantou University Medical College, Shantou, China.
He
Shaoheng
S
D002469:Cell Separation; D006801:Humans; D007249:Inflammation / Q000276:immunology; D015850:Interleukin-6 / Q000276:immunology / Q000378:metabolism*; D010455:Peptides / Q000494:pharmacology; D044462:Receptors, Proteinase-Activated / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D012697:Serine Endopeptidases / Q000378:metabolism*; D015842:Serine Proteinase Inhibitors / Q000494:pharmacology; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism*
D015850:Interleukin-6; D010455:Peptides; D044462:Receptors, Proteinase-Activated; D015842:Serine Proteinase Inhibitors; D012697:Serine Endopeptidases