H2O2 Is an Important Mediator of Physiological and Pathological Healing Responses

Background. TGF-β1 is a pleiotropic cytokine that plays a key role in wound healing and organ fibrosis. We have recently demonstrated that, in part, some fibrogenic actions of TGF-β1 are mediated via formation of H2O2. We have also demonstrated that TGF-β1 plays a key role in the accelerated healing response induced by a peptidoglycan derived from some strains of Staphylococcus aureus (SaPG). s. To investigate further the role of H2O2 in healing responses, we implemented and improved a method to measure this reactive oxygen species. Using 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 alcohol sponges that had been surgically subcutaneously implanted in the dorsum of rats. s. We show that cultured hepatic stellate cells produce significant amounts of H2O2. We show also that H2O2 formation by saline- and SAPG-inoculated sponges is more intense during the early inflammatory phase of the healing response and precedes collagen deposition. Moreover, the production of H2O2 is much higher in SaPG-inoculated sponges than in those inoculated with saline solution. sions. Based on these findings, and on the fact that H2O2 is produced during TGF-β-induced upregulation of the α1(I) procollagen gene, we conclude that H2O2 is one of the mediators of healing responses.