Reply

Abstract

Reply: Protease-activated receptors (PARs, namely, PAR-1, PAR-2, PAR-3, and PAR-4) have been shown to play an important role in the interplay between inflammation and coagulation (1-3). Protease-activated receptor 2, actively involved in both inflammation and the immune response (2, 4), has been found to be also expressed in various structures of the kidney (5). Our several publications have already clearly identified the expression of PAR-2 in various organs in sepsis. To further clarify the role of PAR-2 in the pathological mechanisms in sepsis, we got the idea to use a PAR-2 blocking peptide from a published article by Matsuda et al. (6). They have demonstrated that pancreatitis-induced increase in pulmonary MIF expression was strongly inhibited by the antibody to PAR-2, a receptor that is activated by trypsin and tryptase (sc-9278 P; Santa Cruz Biotechnology, Santa Cruz, Calif) (6). The anti-PAR-2 antibody also showed a strong inhibition of the pancreatitis-induced increase in Toll-like receptor 4 mRNA expression in the same report (6). Our very recent study has used the same Santa Cruz Biotechnology (sc-9278 P) product and presented the findings obtained from the experimental result (7). What we wanted to convey in that report is that PAR-2 may be a potential therapeutic target for the renal impairment in sepsis (7). This report cannot certainly rule out whether the observed beneficial effect of sc-9278 P results from the direct or indirect effect mediated through PAR-2. Our article has also clearly demonstrated the limitations and drawbacks of using sc-9278 P (7). We completely agree with the idea that the detrimental role of PAR-2 in acute renal failure needs to be confirmed using alternative approaches, like, for instance, the use of PAR-2-deficient mice, which is currently ongoing in our laboratory. The authors wholeheartedly thank Spek et al. for the letter to the editor concerning their comment on PAR-2 in renal impairment in sepsis. Subrina Jesmin Satoshi Gando International Medical Center of Japan and Hokkaido University Graduate School of Medicine Japan