TAK-242 ameliorates contact dermatitis exacerbated by IL-36 receptor antagonist deficiency View Full Text


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Article Info

DATE

2020-01-20

AUTHORS

Hidehiko Fukushima, Yohei Iwata, Soichiro Watanabe, Kenta Saito, Yoshihito Tanaka, Yurie Hasegawa, Masashi Akiyama, Kazumitsu Sugiura

ABSTRACT

Loss-of-function mutations in IL36RN cause generalized pustular psoriasis (GPP), which is characterized by neutrophil-infiltrated lesions. Neutrophils are important during contact hypersensitivity in mice. However, it has never been determined whether interleukin-36 receptor antagonist (IL-36Ra) deficiency is an exacerbating factor in contact dermatitis. We examined whether a loss-of-function IL36RN mutation exacerbates contact dermatitis and evaluated the changes in contact dermatitis-related cytokines. Wild-type and Il36rn-/- mice were treated with 1-fluoro-2,4-dinitorobenzene (DNFB) and evaluated for ear thickness, histopathological features, numbers of infiltrated neutrophils, and numbers of CD4 + and CD8 + T cells. Furthermore, mRNA levels of contact dermatitis-related cytokines were measured by real-time polymerase chain reaction, and effects of TAK-242, a toll-like receptor 4 (TLR4) inhibitor, on the contact hypersensitivity (CHS) response were evaluated. We found that the ear thickness, cytokine expression, and neutrophil infiltration significantly increased in Il36rn-/- mice compared with that in wild-type mice. TAK-242 alleviated CHS and prevented neutrophil infiltration, cytokine expression, and ear thickening in Il36rn-/- mice. These data indicate that Il36rn-/- mutations are an exacerbating factor for CHS and that TAK-242 can reduce the inflammatory responses that are associated with the CHS response. More... »

PAGES

734

References to SciGraph publications

  • 2009-09-18. Skin immune sentinels in health and disease in NATURE REVIEWS IMMUNOLOGY
  • <error retrieving object. in <ERROR RETRIEVING OBJECT
  • 2015-10-22. Aquaporin-9-expressing neutrophils are required for the establishment of contact hypersensitivity in SCIENTIFIC REPORTS
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    http://scigraph.springernature.com/pub.10.1038/s41598-020-57550-5

    DOI

    http://dx.doi.org/10.1038/s41598-020-57550-5

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1124189622

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/31959814


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