Involvement of thromboxane A2 in interleukin-31-induced itch-associated response in mice
저자 | Andoh, Tsugunobu ⁎ Li, Sikai Uta, Daisuke |
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자료유형 | Article |
초록 | •Interleukinin-31 (IL-31) induced scratching, an itch-associated response, in mice.•IL-31-induced scratching was inhibited by TP thromboxane (TX) receptor antagonist.•IL-31 receptors were expressed mainly in epidermal keratinocytes.•IL-31 induced TXA2 production in the skin and primary cultures of keratinocytes.•The results suggest that IL-31 elicits scratching via epidermal TXA2 production. Background Atopic dermatitis is a chronic and severe pruritic skin disease. Interlukin-31 (IL-31) has been recently demonstrated to be one of the key pruritogens in atopic dermatitis. However, the mechanisms underlying IL-31-induced itching remains unclear. In our previous study, we have shown that thromboxane (TX) A2 is involved in itch-associated responses in mice with atopy-like skin diseases. Methods IL-31 was given intradermally into the rostral back of ICR mice and the hind-paw scratching to the injection site were counted. Expression of TX synthase and IL-31 receptors were analyzed using immunohistochemical staining or RT-PCR in mouse skin or primary cultures of mouse keratinocytes. The concentration of TXB2, a metabolite of TXA2, in the skin and the culture medium of primary cultures of mouse keratinocytes was measured using enzyme immunoassay. The concentration of intracellular Ca2+ ions in mouse keratinocytes was measured using the calcium imaging method. Results An intradermal injection of IL-31 elicited scratching, an itch-related response, in mice. The scratching was inhibited by TP TXA2 receptor antagonist DCHCH. The distribution of TX synthase and IL-31RA receptor was mainly epidermal keratinocytes in the skin. The primary cultures of keratinocytes expressed the mRNAs of TX synthase and IL-31 receptors. IL-31 increased the concentration of TXB2, which was inhibited by TX synthase inhibitor sodium ozagrel and EGTA, in the skin and the culture medium of primary cultures of keratinocytes. IL-31 increased the concentration of intracellular Ca2+ ions in mouse keratinocytes. Conclusion It is suggested that IL-31 elicits itch-associated responses through TXA2 produced from keratinocytes. |
Affiliation | Department of Applied Pharmacology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama 930-0194, Japan |
Publisher | Elsevier Urban & Partner Sp. z o.o. |
DOI | 10.1016/j.pharep.2017.10.001 |
Accession Number | S1734114017303808 |
Copyright | © 2017 Published by Elsevier Sp. z o.o. on behalf of Institute of Pharmacology, Polish Academy of Sciences. |
Involvement of thromboxane A2 in interleukin-31-induced itch-associated response in mice