Potential inhibition of 12- O -tetradecanoylphorbol-13-acetate-induced inflammation, hyperproliferation, and hyperplasiogenic responses by celecoxib in mouse skin.

Purpose: Skin exposure to noxious agents leads to cutaneous lesion marked by an increase in inflammation, cellular proliferation, and hyperplasiogenic reactions. Studies have demonstrated that these damages breach the skin integrity resulting in the etiology of various cutaneous disorders like atopic dermatitis, eczema, psoriasis, and development of non-melanoma skin cancer. Celecoxib, a cyclooxygenase- 2 (COX-2) inhibitor, is an effective treatment for a variety of inflammatory diseases. Its importance in the therapy of skin problems, however, remains underappreciated. Methods: We tested topically applied celecoxib on skin inflammation, cellular proliferation, and hyperplasia induced by the phorbol ester 12- O -tetradecanoylphorbol-13-acetate (TPA) in Swiss albino mice. Results: Celecoxib (5 and 10 μmol) markedly reduced TPA (10 nmol) induced prostaglandin E 2 (PGE 2 ) production, edema formation, myeloperoxidase (MPO) activity, and levels of pro-inflammatory cytokines such as tumour necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), and interleukin-6 (IL-6). It also resulted in a considerable decrease in ornithine decarboxylase (ODC) activity and the incorporation of [ 3 H]-thymidine into DNA. In addition, there was a significant improvement in histoarchitectural abnormalities such as epidermal thickness, number of epidermal cell layers, neutrophil infiltration, intercellular edema, and vasodilation. Conclusion: Our results demonstrates that topical celecoxib can reduce the inflammation, hyperproliferation, and hyperplasiogenic events of skin insults suggesting that it may prove to be a valuable management option for cutaneous lesion and associated illnesses such as atopic dermatitis, eczema, and psoriasis, as well as the emergence of non-melanoma cancer.