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Increased M1 macrophages in young miR‐15a/16 −/− mice with tumour grafts or dextran sulphate sodium‐induced colitis
Author(s) -
Jia Xiaoqin,
Hu Xiangyu,
Han Sen,
Miao Xin,
Liu Hao,
Li Xiaomin,
Lin Zhijie,
Wang Zhengbing,
Gong Weijuan
Publication year - 2018
Publication title -
scandinavian journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.934
H-Index - 88
eISSN - 1365-3083
pISSN - 0300-9475
DOI - 10.1111/sji.12703
Subject(s) - proinflammatory cytokine , colitis , lipopolysaccharide , macrophage polarization , inflammation , stat3 , hmgb1 , cancer research , macrophage , chemistry , microrna , m2 macrophage , immunology , biology , microbiology and biotechnology , phosphorylation , biochemistry , gene , in vitro
M1 macrophages are involved in inflammation by producing proinflammatory cytokines, whereas M2 macrophages are associated with wound healing and tissue regeneration by producing anti‐inflammatory cytokines. Micro RNA s are involved in macrophage polarization. To evaluate whether miR‐15a/16 is involved in macrophage polarization under tumour or inflammation microenvironments, we observed the growth of transplanted hepatic cancer (H22) cells or severity of dextran sulphate sodium ( DSS )‐induced colitis in 8‐week‐old miR‐15a/16 knockout ( KO ) mice. Compared with littermate controls, the miR‐15a/16 −/− mice exhibited retarded tumour growth and increased sensibility to DSS ‐induced colitis. Meanwhile, the M1 cell frequencies were higher in tumour tissues and inflamed colons of KO mice than of littermate controls. Macrophages with miR‐15a/16 deletion revealed an enhanced NF ‐κB transcription under the physiological state and lipopolysaccharide ( LPS ) or high mobility group box 1 ( HMGB 1) stimulation. STAT 3 expression was also significantly increased in miR‐15a/16 −/− macrophages under LPS or HMGB 1 stimulation. The polarization of M1 macrophages can be associated with the coactivation of NF ‐κB and STAT 3. Results indicated that miR‐15a/16 deficiency in the macrophages directs M1 polarization for tumour suppression and proinflammation. Thus, miR‐15a/16 deletion in macrophages holds a distinct biological significance from that of the micro RNA deficiency in tumour cells.