IL-33/ST2 induces neutrophil-dependent reactive oxygen species production and mediates gout pain.
作者： Chengyu Yin , Boyu Liu , Yuanyuan Li , Xiaojie Li , Jie Wang
DOI: 10.7150/THNO.48028
关键词:
摘要: Objective: Gout, induced by monosodium urate (MSU) crystal deposition in joint tissues, provokes severe pain and impacts life quality of patients. However, the mechanisms underlying gout are still incompletely understood. Methods: We established a mouse model intra-articularly injection MSU crystals into ankle wild type genetic knockout mice. RNA-Sequencing, vivo molecular imaging, Ca2+ reactive oxygen species (ROS) generation, neutrophil influx nocifensive behavioral assays, etc. were used. Results: found interleukin-33 (IL-33) was among top up-regulated cytokines inflamed ankle. Neutralizing or deletion IL-33 its receptor ST2 (suppression tumorigenicity) significantly ameliorated hypersensitivities inflammation. Mechanistically, largely released from infiltrated macrophages upon stimulation. promoted triggered neutrophil-dependent ROS production via during gout, which turn, activated transient potential ankyrin 1 (TRPA1) channel dorsal root ganglion (DRG) neurons produced nociception. Further, TRPA1 activity enhanced DRG that innervate dependent mechanism, results exaggerated nociceptive response to endogenous products gout. Conclusions: demonstrated previous unidentified role IL-33/ST2 mediating hypersensitivity inflammation through promoting activation. Targeting may represent novel therapeutic approach ameliorate
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