Inhibition of Wound TGF Beta-1 by Celecoxib: A Possible Therapeutic Route for Scar Free Wound

Background: Wound healing is a highly ordered dynamic process associated with inflammation at early stages and with permanent scarring at late stages. Scars could be disfiguring and could advance to be hypertrophic or keloid scars, this would have a strong physical and psychological impact on the patients afterward. The role of inflammatory mediators which could be pro- or anti-inflammatory, pro-or antifibrotic was the focus of wound healing research for decades and the balance between them is the key factor determining the outcome of healing.Aims: In this study, we investigate the correlation and the interrelation between the pro-inflammatory Cyclooxygenase-2 (COX-2) and the pro fibrotic (TGF-Beta-1) in an in vivo model of incisional dermal wound healing and the effect of a selective COX-2 inhibiton the progression of repair and scar formation.Materials and methods: Adult male Sprague-Dawley rats received four full thickness dermal wounds. a selective COX-2 inhibitor was applied to the wounds immediately postwounding twice daily for two days. Wounds and scars were then harvested and at different time points and processed for COX-2 and TGF Beta-1 immunostaining and for collagen staining. Immunoreactivity was semi quantified using Image J.Results: We have shown upregulation of COX-2, co-upregulation and colocalization of TGF-Beta-1 and COX-2 two days postwounding during the inflammatory phase. Celecoxib application significantly inhibited both COX- 2 (P<0.01) and TGF Beta-1 (P<0.001). It improved wound healing microscopically and macroscopically, through reducing inflammatory cell infiltrate, granulation tissues formation and early closure of the incision. Additionally, there was marked improvement in the postwounding scarring. There was a significantly (P<0.01) correlation between COX-2 and TGF Beta-1 (Pearson Correlation=0.94).Conclusion: The overall effect of COX-2 inhibitor was shortening of the inflammatory phase of wound healing with subsequent minimization of the associated tissue destruction and consequently improvement of the scar quality. COX-2 inhibitors regulate inflammatory phase of the wound. They could regulate collagen deposition byregulating the produc-tion of the pro fibrotic TGF Beta-1 production, through autocrine/paracrine effect. Therefore, early application of COX-2 inhibitors to wounds immediately after injury/surgery could enhance the repair and improve the quality of scar.