Hesperidin ameliorates lipopolysaccharide-induced acute lung injury in mice by inhibiting HMGB1 release.
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-α (TNF-α), 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-α 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.
Department of Immunology, School of Medicine, Yangtze University, Jingzhou 434023, People's Republic of China.
Xin-xin
XX
Liu
Department of Immunology, School of Medicine, Yangtze University, Jingzhou 434023, People's Republic of China.
Dan-dan
DD
Yu
Department of Immunology, School of Medicine, Yangtze University, Jingzhou 434023, People's Republic of China.
Mao-jian
MJ
Chen
Department of Immunology, School of Medicine, Yangtze University, Jingzhou 434023, People's Republic of China.
Ting
T
Sun
Department of Immunology, School of Medicine, Yangtze University, Jingzhou 434023, People's Republic of China.
Gang
G
Li
Department of Immunology, School of Medicine, Yangtze University, Jingzhou 434023, People's Republic of China.
Wen-jian
WJ
Huang
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.
Hao
H
Nie
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.
Chao
C
Wang
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.
Yan-xiang
YX
Zhang
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.
Quan
Q
Gong
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.
Bo-xu
BX
Ren
D055371:Acute Lung Injury / Q000188:drug therapy* / Q000378:metabolism; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002452:Cell Count; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000378:metabolism; D024243:HMGB1 Protein / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D006569:Hesperidin / Q000494:pharmacology* / Q000627:therapeutic use*; D015850:Interleukin-6 / Q000378:metabolism; D008070:Lipopolysaccharides; D017737:Macrophages, Peritoneal / Q000378:metabolism; D008297:Male; D008807:Mice, Inbred BALB C; D009195:Peroxidase / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D024243:HMGB1 Protein; C582808:HMGB1 protein, mouse; D015850:Interleukin-6; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; C577686:interleukin-6, mouse; D006569:Hesperidin; D009195:Peroxidase
Acute lung injury; Hesperidin; High-mobility group box 1; MCP-1; Macrophage; TNF-α