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Curcumin inhibits epigen and amphiregulin upregulated by 2,4,6-trinitrochlorobenzene associated with attenuation of skin swelling

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Abstract

Objectives

Contact dermatitis model involving repeated application of hapten is used as a tool to assess dermatitis, as characterized by thickening. Involvement of cell proliferation, elicited by repeated hapten-stimulation, in this swelling has been unclear. Curcumin is reported to reduce inflammation. We examined involvement of cell proliferation and the role of extracellular regulated kinase (ERK) in 2,4,6-trinitrochlorobenzene (TNCB) challenge-induced ear swelling. We also examined the effects of curcumin in this model.

Methods

Mice were sensitized with TNCB to the abdominal skin. Then, they were challenged with TNCB to the ear three times. The ERK activation inhibitor U0126 or curcumin was applied 30 min before each TNCB challenge.

Results

TNCB challenge-induced increased epidermal cell number and dermal thickening. Gene expressions of epithelial mitogen (EPGN), amphiregulin (AREG) and heparin-binding-epidermal growth factor (HB-EGF) were increased in the ears after the last TNCB challenge. Ki-67 immunoreactivity was increased in the dermis in TNCB-challenged ears. TNCB-induced swelling was inhibited by U0126 and curcumin. Curcumin also attenuated TNCB-induced ERK phosphorylation and expression of EPGN and AREG genes.

Conclusion

Ear swelling induced by TNCB challenge might be mediated, in part, by the EPGN- and AREG-ERK proliferation pathway and was inhibited by curcumin.

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Acknowledgements

We thank Ms. Yuka Inoue for technical assistance. This work was supported by Grants from the MEXT-Supported Program for the Strategic Research Foundation at Private Universities (2014–2018, S1411019) and KAKENHI (15K18880) by a Grant-in-Aid for Young Scientists (B) from the Japan Society for the Promotion of Science.

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Authors and Affiliations

  1. Division of Pharmacy Professional Development and Research, Department of Analytical Pathophysiology, School of Pharmacy, Hoshi University, 2-4-41 Ebara, Shinagawa-ku, Tokyo, 142-8501, Japan

    Hiroyasu Sakai, Ken Sato, Fumiaki Sato, Yuki Kai & Tetsuro Yumoto

  2. Department of Pharmacology, School of Pharmacy, Hoshi University, 2-4-41 Ebara, Shinagawa-ku, Tokyo, 142-8501, Japan

    Kazutaka Mandokoro & Minoru Narita

  3. Division of Pathological Sciences, Department of Pharmacology and Experimental Therapeutics, Kyoto Pharmaceutical University, Yamashina, Kyoto, 607-8414, Japan

    Kenjiro Matsumoto & Shinichi Kato

  4. Department of Physiology and Molecular Sciences, School of Pharmacy, Hoshi University, 2-4-41 Ebara, Shinagawa-ku, Tokyo, 142-8501, Japan

    Yoshihiko Chiba

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  1. Hiroyasu Sakai
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  2. Ken Sato
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  3. Fumiaki Sato
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Correspondence to Hiroyasu Sakai.

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Sakai, H., Sato, K., Sato, F. et al. Curcumin inhibits epigen and amphiregulin upregulated by 2,4,6-trinitrochlorobenzene associated with attenuation of skin swelling. Inflamm. Res. 66, 663–678 (2017). https://doi.org/10.1007/s00011-017-1048-0

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  • DOI: https://doi.org/10.1007/s00011-017-1048-0

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