18Beta-glycyrrhetinic acid ameliorates acute Propionibacterium acnes-induced liver injury through inhibition of macrophage inflammatory protein-1alpha.
18Beta-glycyrrhetinic acid (GA), the major bioactive component of licorice root extract, has a protective effect on hepatic injury and exhibits antiinflammatory activity. Here, we investigate the effect of GA in Propionibacterium acnes-induced acute inflammatory liver injury. C57BL/6 mice were primed with P. acnes followed by lipopolysaccharide challenge to induce fulminant hepatitis. GA (75 mg/kg) or vehicle control was administered intraperitoneally daily 1 day after P. acnes priming, and GA significantly improved mouse mortality. Then, to investigate the underlying mechanisms of GA in this acute inflammatory liver injury model, we primed C57BL/6 mice with P. acnes only. We propose that GA ameliorates acute P. acnes-induced liver injury through reduced macrophage inflammatory protein (MIP)-1alpha expression in Kupffer cells by down-regulating MyD88 expression and inhibiting NF-kappaB activation. Reduced MIP-1alpha expression lowered the recruitment of CD11c(+)B220(-) dendritic cell precursors into the liver. Consequently, GA treatment inhibits the activation and proliferation of liver-infiltrating CD4(+) T cells and reduces the production of serum alanine aminotransferase and proinflammatory cytokines such as interferon-gamma and tumor necrosis factor-alpha. Moreover, anti-MIP-1alpha treatment in P. acnes-primed mice inhibits the recruitment of dendritic cell precursors into the liver and suppresses mouse mortality as GA does. Taken together, our results suggest that GA exhibits antiinflammatory effects through inhibition of MIP-1alpha in a mouse model of acute P. acnes-induced inflammatory liver injury.
Xiao
Yichuan
Y
Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Chinese Academy of Sciences, Shanghai 200025, China.
Xu
Jingwei
J
Mao
Chaoming
C
Jin
Min
M
Wu
Qiong
Q
Zou
Jie
J
Gu
Qiaoli
Q
Zhang
Yi
Y
Zhang
Yanyun
Y
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000737:chemistry / Q000494:pharmacology*; D039521:CD11c Antigen / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002465:Cell Movement / Q000187:drug effects / Q000276:immunology; D054405:Chemokine CCL3 / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology; D004365:Drugs, Chinese Herbal / Q000737:chemistry; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects / Q000276:immunology; D006034:Glycyrrhetinic Acid / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D006035:Glycyrrhiza / Q000737:chemistry; D016908:Gram-Positive Bacterial Infections / Q000188:drug therapy* / Q000276:immunology; D006520:Hepatitis, Animal / Q000188:drug therapy* / Q000276:immunology; D007371:Interferon-gamma / Q000276:immunology; D007728:Kupffer Cells / Q000276:immunology*; D017493:Leukocyte Common Antigens / Q000276:immunology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008099:Liver / Q000276:immunology; D017114:Liver Failure, Acute / Q000188:drug therapy* / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D051379:Mice; D053594:Myeloid Differentiation Factor 88 / Q000276:immunology; D018517:Plant Roots / Q000737:chemistry; D011425:Propionibacterium acnes / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
D000893:Anti-Inflammatory Agents; D039521:CD11c Antigen; C496534:Ccl3 protein, mouse; D054405:Chemokine CCL3; D004365:Drugs, Chinese Herbal; D008070:Lipopolysaccharides; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D014409:Tumor Necrosis Factor-alpha; C119129:18alpha-glycyrrhetinic acid; D007371:Interferon-gamma; D017493:Leukocyte Common Antigens; D006034:Glycyrrhetinic Acid