Journal of Inflammation Research (Aug 2023)
Suppression of P2X7R by Local Treatment Alleviates Acute Gouty Inflammation
Abstract
Yang Zhao,1– 3 Zhiyuan Li,2 Ying Chen,3– 5 Yushuang Li,3– 5 Jie Lu2– 5 1Department of Orthodontics, the Affiliated Hospital of Qingdao University, Qingdao, People’s Republic of China; 2Medical Research Center, the Affiliated Hospital of Qingdao University, Qingdao, People’s Republic of China; 3Shandong Provincial Key Laboratory of Metabolic Diseases and Qingdao Key Laboratory of Gout, the Affiliated Hospital of Qingdao University, Qingdao, People’s Republic of China; 4Shandong Provincial Clinical Research Center for Immune Diseases and Gout, the Affiliated Hospital of Qingdao University, Qingdao, People’s Republic of China; 5Department of Endocrinology and Metabolism, the Affiliated Hospital of Qingdao University, Qingdao, People’s Republic of ChinaCorrespondence: Jie Lu, Shandong Provincial Key Laboratory of Metabolic Diseases and Qingdao Key Laboratory of Gout, the Affiliated Hospital of Qingdao University, 16 Jiangsu Road, Qingdao, Shandong, 266003, People’s Republic of China, Tel +86 17853297395, Fax +86 0532-82912019, Email [email protected]: Gout is the most common inflammatory arthritis associated with interleukin-1β (IL-1β) accumulation during exacerbation. In this study, we aimed to clarify whether potassium channel antagonists attenuate local inflammation in mice with monosodium urate (MSU)-induced gout.Methods: We cultured human macrophage THP-1 cells and evaluated the molecular levels of both IL-1β and potassium channels stimulated with MSU and/or potassium channel antagonists. Acute gout models were generated in IL-1β luciferase transgenic male mice using synovium-like subcutaneous air pouches with MSU injection. Their luciferase activities were monitored following potassium channel blocker treatment using the IVIS Spectrum CT imaging system. The lavages and tissues were extracted from their air pouches, followed by cell counting and pathological analysis.Results: MSU stimulation increased the gene expression levels of pro-IL-1β, P2x7r and Kv1.3, whereas the expression of Kcnq1 was decreased in phorbol 12-myristate 13-acetate-induced THP-1 cells. Both high and low concentrations of the P2x7 receptor inhibitor adenosine 5′-triphosphate (ATP) derivative periodate oxidized ATP (oATP) decreased the production of IL-1β in the supernatant of THP-1 cells. The sixth hour was the peak time of IL-1β luciferase activity after MSU intervention in vivo. oATP ameliorated the synovial IL-1β luciferase activity, reduced inflammatory cell infiltration and alleviated the erosive damage in the cartilage.Conclusion: The anti-inflammatory properties of potassium channel inhibitors, especially of oATP, might point to new strategies for local anti-inflammatory therapy for acute gout.Keywords: acute gout, interleukin-1β, potassium channel, local treatment
