TAILIEUCHUNG - Báo cáo khoa học: The chromosomal protein HMGN2 mediates lipopolysaccharide-induced expression of b-defensins in A549 cells

Humanb-defensin-2 (HBD-2) is an antimicrobial peptide produced by the epithelial cells that plays an important role in innate and adaptive immu-nity. Here we report that high mobility group protein N2 (HMGN2), a member of the high mobility group superfamily that affects chromatin function, modulates the expression of HBD-2 in A549 cells treated by lipo-polysaccharide. | 1FEBS Journal The chromosomal protein HMGN2 mediates lipopolysaccharide-induced expression of b-defensins in A549 cells Lu-Xia Deng1 2 Gui-Xia Wu1 Yue Cao1 Bo Fan1 Xiang Gao1 Lin Luo3 and Ning Huang1 4 1 Research Unit of Infection and Immunity West China Schoolof Preclinicaland Forensic Medicine Sichuan University Chengdu China 2 Chongqing Lummy PharmaceuticalCo. Ltd Chongqing China 3 Department of Anesthesiology West China College of Stomatology Sichuan University Chengdu China 4 State Key Laboratory of Biotherapy West China Hospital Sichuan Chengdu China Keywords high mobility group protein N2 human b-defensin-2 lipopolysaccharide p65 regulation Correspondence N. Huang Research Unit of Infection and Immunity West China Schoolof Preclinical and Forensic Medicine Sichuan University Chengdu China Fax Tel 86 28 8506 8208 E-mail huangpanxiao@ Received 13 August 2010 revised 5 April 2011 accepted 11 April 2011 doi Human b-defensin-2 HBD-2 is an antimicrobial peptide produced by the epithelial cells that plays an important role in innate and adaptive immunity. Here we report that high mobility group protein N2 HMGN2 a member of the high mobility group superfamily that affects chromatin function modulates the expression of HBD-2 in A549 cells treated by lipopolysaccharide. Mechanistically HMGN2 prolongs the retention time and enhances the accumulation of nuclear factor kB p65 in the nucleus and promotes the acetylation of p65 through increasing histone acetyltransferase activity and enhancing p65-Ser536 phosphorylation. Additionally chromatin immunoprecipitation reveals that HMGN2 and p65 synergistically promote their specific binding to HBD-2 promoter thereby affecting the downstream transcription. Taken together these results suggest that HMGN2 acts as a positive modulator of nuclear factor kB signalling to promote lipopolysaccharide-induced b-defensin expression. Introduction Antimicrobial peptides are produced by many different

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