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MSU crystals have been demonstrated in skin diseases such as tophaceous gout or psoriasis; however, the importance of MSU crystals in the skin is totally unknown. In this study, we found that MSU crystals, through P2Y6 receptors, stimulated normal human keratinocytes (NHK) to produce IL-1\u03b1, IL-8\/CXCL8, and IL-6. P2Y6 receptor expression increased in MSU-stimulated NHK. Both P2Y6-specific antagonist and P2Y6 antisense oligonucleotides significantly inhibited the production of IL-1\u03b1, IL-8\/CXCL8, and IL-6 by NHK. Similarly, the P2Y6-specific antagonist completely inhibited the MSU-induced production of IL-1\u03b2 by THP-1 cells, a human monocytic cell line. Remarkably, the P2Y6-specific antagonist significantly reduced neutrophil influx in both mouse air pouch and peritonitis models. Thus, these results indicate that the P2Y6 receptor signaling pathway may be a potential therapeutic target for MSU-associated inflammatory diseases, such as tophaceous gout.<\/jats:p>","DOI":"10.4049\/jimmunol.1003746","type":"journal-article","created":{"date-parts":[[2011,11,19]],"date-time":"2011-11-19T05:56:16Z","timestamp":1321682176000},"page":"436-444","source":"Crossref","is-referenced-by-count":82,"title":["P2Y6 Receptor Signaling Pathway Mediates Inflammatory Responses Induced by Monosodium Urate Crystals"],"prefix":"10.1093","volume":"188","author":[{"given":"Hideya","family":"Uratsuji","sequence":"first","affiliation":[{"name":"Department of Dermatology, Graduate School of Medicine, University of Tokyo , Tokyo 113-8655 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yayoi","family":"Tada","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Graduate School of Medicine, University of Tokyo , Tokyo 113-8655 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomohiko","family":"Kawashima","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Graduate School of Medicine, University of Tokyo , Tokyo 113-8655 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masahiro","family":"Kamata","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Graduate School of Medicine, University of Tokyo , Tokyo 113-8655 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carren Sy","family":"Hau","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Graduate School of Medicine, University of Tokyo , Tokyo 113-8655 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshihide","family":"Asano","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Graduate School of Medicine, University of Tokyo , Tokyo 113-8655 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Makoto","family":"Sugaya","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Graduate School of Medicine, University of Tokyo , Tokyo 113-8655 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takafumi","family":"Kadono","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Graduate School of Medicine, University of Tokyo , Tokyo 113-8655 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akihiko","family":"Asahina","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Sagamihara National Hospital , Kanagawa 252-0392 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shinichi","family":"Sato","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Graduate School of Medicine, University of Tokyo , Tokyo 113-8655 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kunihiko","family":"Tamaki","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Graduate School of Medicine, University of Tokyo , Tokyo 113-8655 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2012,1,1]]},"reference":[{"key":"2025032409415698000_r1","doi-asserted-by":"crossref","first-page":"2262","DOI":"10.1172\/JCI28075","article-title":"MyD88-dependent IL-1 receptor signaling is essential for gouty inflammation stimulated by monosodium urate crystals","volume":"116","author":"Chen","year":"2006","journal-title":"J. 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