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Here, we demonstrate that glycolysis is linked to the proinflammatory activation of human blood monocyte-derived macrophages in ankylosing spondylitis. Specifically, ankylosing spondylitis macrophages produced excessive inflammation, including TNF\u03b1, IL1\u03b2, and IL23, and displayed an overactive status by exhibiting stronger costimulatory signals, such as CD80, CD86, and HLA-DR. Moreover, we found that patient-derived monocyte-derived M1-type macrophages (M1 macrophages) exhibited intensified glycolysis, as evidenced by a higher extracellular acidification rate. Upregulation of PKM2 and GLUT1 was observed in ankylosing spondylitis\u2013derived monocytes and monocyte-derived macrophages, especially in M1 macrophages, indicating glucose metabolic alteration in ankylosing spondylitis macrophages. To investigate the impact of glycolysis on macrophage inflammatory ability, we treated ankylosing spondylitis M1 macrophages with 2 inhibitors: 2-deoxy-D-glucose, a glycolysis inhibitor, and shikonin, a PKM2 inhibitor. Both inhibitors reduced proinflammatory function and reversed the overactive status of ankylosing spondylitis macrophages, suggesting their potential utility in treating the disease. These data place PKM2 at the crosstalk between glucose metabolic changes and the activation of inflammatory macrophages in patients with ankylosing spondylitis.<\/jats:p>","DOI":"10.1093\/jleuko\/qiad054","type":"journal-article","created":{"date-parts":[[2023,5,16]],"date-time":"2023-05-16T18:29:37Z","timestamp":1684261777000},"page":"595-603","source":"Crossref","is-referenced-by-count":21,"title":["PKM2 promotes proinflammatory macrophage activation in ankylosing spondylitis"],"prefix":"10.1093","volume":"114","author":[{"given":"Weizhen","family":"Weng","sequence":"first","affiliation":[{"name":"Department of Rheumatology and Immunology, Third Affiliated Hospital of Sun Yat-sen University , 600 Tianhe Road, Tianhe District, Guangzhou , China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yanli","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Immunology, Third Affiliated Hospital of Sun Yat-sen University , 600 Tianhe 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