PMID- 25724384 OWN - NLM STAT- MEDLINE DCOM- 20160104 LR - 20150324 IS - 1878-1705 (Electronic) IS - 1567-5769 (Linking) VI - 25 IP - 2 DP - 2015 Apr TI - Hesperidin ameliorates lipopolysaccharide-induced acute lung injury in mice by inhibiting HMGB1 release. PG - 370-6 LID - S1567-5769(15)00069-7 [pii] LID - 10.1016/j.intimp.2015.02.022 [doi] AB - Hesperidin (HDN), a flavanone glycoside, possesses anti-inflammatory properties and has been suggested to be able to modulate the lipopolysaccharide (LPS)-induced acute lung injury (ALI). High-mobility group box 1 (HMGB1) serves as an inflammatory cytokine when released extracellularly and is involved in the pathogenesis of diverse inflammatory disorders. The current study aimed to investigate the involvement of HMGB1 in HDN-induced immunoregulation of ALI. ALI in male BALB/c mice was induced by intranasal administration of LPS (0.5mg/kg). HDN (500mg/kg) was administered intragastrically 10days prior to LPS exposure. HDN significantly protected animals from LPS-induced ALI as evidenced by decreased elevation of the lung wet to dry weight ratio, total cells, neutrophils, macrophages, and myeloperoxidase (MPO) activity, associated with reduced lung histological damage. In the meantime, HDN pretreatment markedly inhibited the production of pro-inflammatory cytokines and chemokine, including tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6) and monocyte chemoattractant protein-1 (MCP-1). Furthermore, HDN pretreatment dramatically inhibited the infiltration of macrophages and suppressed the expression and release of HMGB1 in vivo and in vitro. In addition, intranasal application of exogenous HMGB1 could result in lung injury which was also alleviated by HDN administration. These results suggest that HDN pretreatment protects mice from LPS-induced ALI via inhibiting the production of TNF-alpha and IL-6. Moreover, we found that HDN could inhibit the expression and release of HMGB1 via suppressing the infiltration of macrophages and production of MCP-1. CI - Copyright (c) 2015 Elsevier B.V. All rights reserved. FAU - Liu, Xin-xin AU - Liu XX AD - Department of Immunology, School of Medicine, Yangtze University, Jingzhou 434023, People's Republic of China. FAU - Yu, Dan-dan AU - Yu DD AD - Department of Immunology, School of Medicine, Yangtze University, Jingzhou 434023, People's Republic of China. FAU - Chen, Mao-jian AU - Chen MJ AD - Department of Immunology, School of Medicine, Yangtze University, Jingzhou 434023, People's Republic of China. FAU - Sun, Ting AU - Sun T AD - Department of Immunology, School of Medicine, Yangtze University, Jingzhou 434023, People's Republic of China. FAU - Li, Gang AU - Li G AD - Department of Immunology, School of Medicine, Yangtze University, Jingzhou 434023, People's Republic of China. FAU - Huang, Wen-jian AU - Huang WJ AD - Department of Immunology, School of Medicine, Yangtze University, Jingzhou 434023, People's Republic of China. FAU - Nie, Hao AU - Nie H AD - Department of Immunology, School of Medicine, Yangtze University, Jingzhou 434023, People's Republic of China; Clinical Molecular Immunology Center, School of Medicine, Yangtze University, Jingzhou 434023, People's Republic of China. FAU - Wang, Chao AU - Wang C AD - Department of Immunology, School of Medicine, Yangtze University, Jingzhou 434023, People's Republic of China; Clinical Molecular Immunology Center, School of Medicine, Yangtze University, Jingzhou 434023, People's Republic of China. FAU - Zhang, Yan-xiang AU - Zhang YX AD - Department of Immunology, School of Medicine, Yangtze University, Jingzhou 434023, People's Republic of China; Clinical Molecular Immunology Center, School of Medicine, Yangtze University, Jingzhou 434023, People's Republic of China. FAU - Gong, Quan AU - Gong Q AD - Department of Immunology, School of Medicine, Yangtze University, Jingzhou 434023, People's Republic of China; Clinical Molecular Immunology Center, School of Medicine, Yangtze University, Jingzhou 434023, People's Republic of China. Electronic address: gongquan1998@163.com. FAU - Ren, Bo-xu AU - Ren BX AD - Molecular Biology Teaching and Research, Microbes and Parasites Teaching and Research, Medical College of Yangtze University, School of Medicine, Yangtze University, Jingzhou 434023, People's Republic of China. Electronic address: boxuren188@163.com. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20150225 PL - Netherlands TA - Int Immunopharmacol JT - International immunopharmacology JID - 100965259 RN - 0 (Ccl2 protein, mouse) RN - 0 (Chemokine CCL2) RN - 0 (HMGB1 Protein) RN - 0 (HMGB1 protein, mouse) RN - 0 (Interleukin-6) RN - 0 (Lipopolysaccharides) RN - 0 (Tumor Necrosis Factor-alpha) RN - 0 (interleukin-6, mouse) RN - E750O06Y6O (Hesperidin) RN - EC 1.11.1.7 (Peroxidase) SB - IM MH - Acute Lung Injury/*drug therapy/metabolism MH - Animals MH - Bronchoalveolar Lavage Fluid/cytology MH - Cell Count MH - Cells, Cultured MH - Chemokine CCL2/metabolism MH - HMGB1 Protein/*antagonists & inhibitors/genetics/metabolism MH - Hesperidin/*pharmacology/*therapeutic use MH - Interleukin-6/metabolism MH - Lipopolysaccharides MH - Macrophages, Peritoneal/metabolism MH - Male MH - Mice, Inbred BALB C MH - Peroxidase/metabolism MH - Tumor Necrosis Factor-alpha/metabolism OTO - NOTNLM OT - Acute lung injury OT - Hesperidin OT - High-mobility group box 1 OT - MCP-1 OT - Macrophage OT - TNF-alpha EDAT- 2015/03/01 06:00 MHDA- 2016/01/05 06:00 CRDT- 2015/03/01 06:00 PHST- 2014/08/18 00:00 [received] PHST- 2015/02/01 00:00 [revised] PHST- 2015/02/12 00:00 [accepted] PHST- 2015/03/01 06:00 [entrez] PHST- 2015/03/01 06:00 [pubmed] PHST- 2016/01/05 06:00 [medline] AID - S1567-5769(15)00069-7 [pii] AID - 10.1016/j.intimp.2015.02.022 [doi] PST - ppublish SO - Int Immunopharmacol. 2015 Apr;25(2):370-6. doi: 10.1016/j.intimp.2015.02.022. Epub 2015 Feb 25.