COX-2 induces T cell accumulation and IFN-γ production during the development of chromium allergy

Abstract

Chromium (Cr) is commonly added into various metal alloys to improve some mechanical properties such as corrosion resistance, strength, and workability. However, Cr is also known to be a metal allergen for some individuals. Metal allergy is a T cell-mediated disease with symptoms of inflammation and swelling that involve inflammatory cytokines and prostaglandins. Hence, suppressing these inflammation paths by using COX-2 inhibitor might be useful in treating Cr allergy. In this study, mice were used with Cr-induced allergy challenge model. The mice were injected with celecoxib once per day for 7 days one hour after the challenge. Footpad samples were stained with haematoxylin and eosin (H&E), and lymphocytes were isolated from popliteal lymph nodes for the flow cytometric analysis. The results show that both prostaglandin E₂ (PGE₂), a known mediator of inflammation, and cyclooxygenases (COX)-2 have important roles in the development of Cr allergy. Further, COX-2 inhibitor, celecoxib, was effective in relieving swelling and inflammation in Cr-allergic mice concordant with suppression of IFN-γ production by CD8⁺ T cells and T cell accumulation in the lymph nodes. Therefore, the inhibition of COX-2 may be a therapeutic target for Cr allergy, and additional molecules in the PGE₂ signalling pathway may also be an effective therapeutic target for the treatment of metal allergy.

Keywords:

• Metal allergy
• chromium
• COX-2
• celecoxib
• inflammation

Acknowledgements

We thank Dr Risako Suzuki, Toru Kawakami, Mariko Kajino, Yunosuke Yasuda, Naohiro Sekikawa, Sayaka Ono, Saki Okabe, Hiroki Ogura, Noriko Umehara, Haruka Sasaki, Tomomi Seki, Tatsuya Watanabe, Hironobu Ito, Shigehito Higuchi, Naoki Sato and Naohiko Iguchi for helpful suggestions and technical assistance.

Authors contributions

R. M. S. performed experiments; K. I designed and performed experiments, analyzed data, and prepared the manuscript. Y. S., M. I., K. S., K. U., N. H., T. N., N. H., and U. K. provided technical support and data discussion.

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This work was supported by JSPS KAKENHI [grant No. 15K19075 (K. I.)].