P2Y6 Receptor Signaling Pathway Mediates Inflammatory Responses Induced by Monosodium Urate Crystals

• DOI: 10.4049/jimmunol.1003746
• Publication Date: 2011-11-19T05:56:16Z
• Authors: Hideya Uratsuji; Yayoi Tada; Tomohiko Kawashima; Masahiro Kamata; Carren Sy Hau; Yoshihide Asano; Makoto Sugaya; Takafumi Kadono; Akihiko Asahina; Shinichi Sato; Kunihiko Tamaki
• Keywords: THP1 cell line

Abstract Gout occurs in individuals with hyperuricemia when monosodium urate (MSU) crystals precipitate tissues and induce acute inflammation via phagocytic cells such as monocytes. MSU have been demonstrated skin diseases tophaceous gout or psoriasis; however, the importance of is totally unknown. In this study, we found that crystals, through P2Y6 receptors, stimulated normal human keratinocytes (NHK) to produce IL-1α, IL-8/CXCL8, IL-6. receptor expression increased MSU-stimulated NHK. Both P2Y6-specific antagonist antisense oligonucleotides significantly inhibited production IL-6 by Similarly, completely MSU-induced IL-1β THP-1 cells, a monocytic cell line. Remarkably, reduced neutrophil influx both mouse air pouch peritonitis models. Thus, these results indicate signaling pathway may be potential therapeutic target for MSU-associated inflammatory diseases, gout.