H2O2 is an important mediator of physiological and pathological healing responses

Background. TGF-beta 1 is a pleiotropic cytokine that plays a key role in w ound healing and organ fibrosis. We have recently demonstrated that, in par t, some fibrogenic actions of TGF-beta 1 are mediated via formation of H2O2 . We have also demonstrated that TGF-beta 1 plays a key role in the acceler ated healing response induced by a peptidoglycan derived from some strains of Staphylococcus aureus (SaPG). Methods. To investigate further the role of H2O2 in healing responses, we i mplemented and improved a method to measure this reactive oxygen species. U sing this method, we quantified the production of H2O2 by cultured hepatic stellate cells-the main cells involved in type I collagen production in the liver-and by saline- and SaPG-inoculated polyvinyl al cohol sponges that h ad been surgically subcutaneously implanted in the dorsum of rats. Results. We show that cultured hepatic stellate cells produce significant a mounts of H2O2. We show also that H2O2 formation by saline- and SAPG-inocul ated sponges is more intense during the early inflammatory phase of the hea ling response and precedes collagen deposition. Moreover, the production of H2O2 is much higher in SaPG-inoculated sponges than in those inoculated wi th saline solution. Conclusions. Based on these findings, and on the fact that H2O2 is produced during TGF-beta-induced upregulation of the alpha(I) procollagen gene, we conclude that H2O2 is one of the mediators of healing responses. (C) 2000 I MSS. Published by Elsevier Science Inc.