Tetrathiomolybdate, a copper chelator inhibited imiquimod-induced skin inflammation in mice

Publication date: Available online 11 August 2018

Source: Journal of Dermatological Science

Author(s): Peng-Yang Hsu, Hsu-Heng Yen, Tao-Hsiang Yang, Che-Chun Su

Abstract

Background

Copper is an essential metal for maintenance of many biological functions; however, excessive amount can induce inflammation and oxidative stress. Tetrathiomolybdate (TM) is a copper chelator for treatment of Wilson's disease, and decreased the severity of autoimmune arthritis in mice.

Objective

In this report, we evaluated the effects of TM in a mouse model for psoriasis.

Methods

Imiquimod-induced psoriasis murine model was used. We applied immunohistochemistry staining and ELISA to determine levels of cytokines in the inflamed skin, splenocytes, and draining lymph nodes. In addition, we used keratinocytes and splenocytes to test the inhibitory effects of TM on cytokine production and activation of transcription factors.

Results

Our results showed that TM significantly reduced cumulative scores, epidermis thickness, and ki-67 expression in the inflamed skin. In addition, TM decreased skin cytokine levels and systemic inflammation. Moreover, TM suppressed activation in keratinocytes and splenocytes with reduction in phosphorylation of Erk1/2 and STAT3.

Conclusion

These findings are strong evidence that TM can inhibit psoriasis in the model.

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