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.