H(2)O(2) is an important mediator of physiological and pathological healing responses.
BACKGROUND
TGF-beta1 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-beta1 are mediated via formation of H(2)O(2). We have also demonstrated that TGF-beta1 plays a key role in the accelerated healing response induced by a peptidoglycan derived from some strains of Staphylococcus aureus (SaPG).


METHODS
To investigate further the role of H(2)O(2) in healing responses, we implemented and improved a method to measure this reactive oxygen species. Using this method, we quantified the production of H(2)O(2) 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.


RESULTS
We show that cultured hepatic stellate cells produce significant amounts of H(2)O(2). We show also that H(2)O(2) 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 H(2)O(2) is much higher in SaPG-inoculated sponges than in those inoculated with saline solution.


CONCLUSIONS
Based on these findings, and on the fact that H(2)O(2) is produced during TGF-beta-induced upregulation of the alpha1(I) procollagen gene, we conclude that H(2)O(2) is one of the mediators of healing responses.
Domínguez-Rosales
J A
JA
Division of Gastroenterology, Hepatology and Nutrition, Marion Bessin Liver Research Center and Departments of Medicine, Albert Einstein College of Medicine/Montefiore Medical Center, Bronx, NY 10461, USA.
Mavi
G
G
Levenson
S M
SM
Rojkind
M
M
D000818:Animals; D002478:Cells, Cultured; D006861:Hydrogen Peroxide / Q000378:metabolism*; D008099:Liver / Q000378:metabolism; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D014945:Wound Healing
D006861:Hydrogen Peroxide