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

Abstract

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 aetiology 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 under appreciated.

Methods

We tested efficacy of topically applied celecoxib in mitigating 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 E₂ (PGE₂) production, oedema 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 [³H]-thymidine into DNA. In addition, there was a significant reduction in histoarchitectural abnormalities such as epidermal thickness, number of epidermal cell layers, neutrophil infiltration, intercellular oedema, and vasodilation.

Conclusion

Our results demonstrate 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.

Keywords:

• Skin lesion
• inflammatory responses
• hyperproliferation
• COX-2 inhibitor
• dermoprotection
• hyperplasia

Disclosure statement

No potential conflict of interest was reported by the author(s).

Author contributions

Shakilur Rahman and Sheikh Raisuddin conceptualised and designed the experiment; Shakilur Rahman performed the experiments, analysed data and drafted the manuscript; Sheikh Raisuddin provided necessary facilities. Rizwanul Haque and Sheikh Raisuddin critically reviewed and revised the manuscript; all authors read and approved the final version of the manuscript.

Data availability statement

Data used to support findings of this study are included within the manuscript and its availability has been disclosed.

Additional information

Funding

The Council of Scientific and Industrial Research (CSIR), Government of India provided a Senior Research Fellowship (SRF) to Shakilur Rahman (Grant No. 09/591/(0077)/2008-EMR-I). Authors are thankful to Sun Pharmaceutical Industries Ltd., Mumbai, India for providing celecoxib as a gift.