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Resolution of inflammation is important for physiological homeostasis. Chronic inflammatory diseases may be caused by abnormal resolution of inflammation. However, what causes a failure of inflammatory resolution is unclear. Here we investigated the involvement of high mobility group box 1 (HMGB1) protein in the control of inflammatory resolution as an ‘anti-resolution factor’. We first confirmed the increased expression of HMGB1 and prostaglandin reductase 1 (PTGR1) in inflammatory conditions and HMGB1-mediated regulation of the expression of PTGR1. The inhibition of phagocytosis by HMGB1 was abrogated by PTGR1 silencing. PTGR1 was a direct target of miR522-3p and its expression was regulated by miRNA-522-3p inhibitor or mimic. Finally, miR-522-3p had an important role in the regulation of PTGR1 expression by HMGB1. The data indicates that HMGB1-miR-522-3p-PTGR1 axis may be involved in the abnormal resolution of inflammation and suggests that this mechanism might be a target for modulation of chronic inflammatory disorder. [ABSTRACT FROM AUTHOR]