Quercetin Protects Mice from ConA-Induced Hepatitis by Inhibiting HMGB1-TLR Expression and Down-Regulating the Nuclear Factor Kappa B Pathway
详细信息    查看全文
  • 作者:Xi Li ; Hong-chun Liu ; Qun-yan Yao ; Bei-li Xu ; Shun-cai Zhang ; Chuan-tao Tu
  • 关键词:quercetin ; hepatitis ; inflammation ; nuclear factor κB ; high ; mobility group box 1 protein ; toll ; like receptor
  • 刊名:Inflammation
  • 出版年:2016
  • 出版时间:February 2016
  • 年:2016
  • 卷:39
  • 期:1
  • 页码:96-106
  • 全文大小:2,235 KB
  • 参考文献:1.Thimme, R., S. Wieland, C. Steiger, J. Ghrayeb, K.A. Reimann, R.H. Purcell, et al. 2003. CD8(+) T cells mediate viral clearance and disease pathogenesis during acute hepatitis B virus infection. Journal of Virology 77: 68–76.PubMedCentral CrossRef PubMed
    2.Rehermann, B., and M. Nascimbeni. 2005. Immunology of hepatitis B virus and hepatitis C virus infection. Nature Reviews Immunology 5: 215–229.CrossRef PubMed
    3.Heneghan, M.A., A.D. Yeoman, S. Verma, A.D. Smith, and M.S. Longhi. 2013. Autoimmune hepatitis. Lancet 382: 1433–1444.CrossRef PubMed
    4.Tiegs, G., J. Hentschel, and A. Wendel. 1992. A T cell-dependent experimental liver injury in mice inducible by concanavalin A. Journal of Clinical Investigation 90: 196–203.PubMedCentral CrossRef PubMed
    5.Ajuebor, M.N., J.A. Carey, and M.G. Swain. 2006. CCR5 in T cell-mediated liver diseases: what’s going on. Journal of Immunology 177: 2039–2045.CrossRef
    6.Kawasuji, A., M. Hasegawa, M. Horikawa, T. Fujita, Y. Matsushita, T. Matsushita, et al. 2006. L-selectin and intercellular adhesion molecule-1 regulate the development of concanavalin A-induced liver injury. Journal of Leukocyte Biology 79: 696–705.CrossRef PubMed
    7.Wang, H., O. Bloom, M. Zhang, J.M. Vishnubhakat, M. Ombrellino, J. Che, et al. 1999. HMG-1 as a late mediator of endotoxin lethality in mice. Science 285: 248–251.CrossRef PubMed
    8.Lotze, M.T., and K.J. Tracey. 2005. High-mobility group box 1 protein (HMGB1): nuclear weapon in the immune arsenal. Nature Reviews Immunology 5: 331–342.CrossRef PubMed
    9.Andersson, U., and K.J. Tracey. 2011. HMGB1 is a therapeutic target for sterile inflammation and infection. Annual Review of Immunology 29: 139–162.PubMedCentral CrossRef PubMed
    10.Musumeci, D., G.N. Roviello, and D. Montesarchio. 2014. An overview on HMGB1 inhibitors as potential therapeutic agents in HMGB1-related pathologies. Pharmacology and Therapeutics 141: 347–357.CrossRef PubMed
    11.Baldwin Jr., A.S. 1996. The NF-kappa B and I kappa B proteins: new discoveries and insights. Annual Review of Immunology 14: 649–683.CrossRef PubMed
    12.Sass, G., S. Heinlein, A. Agli, R. Bang, J. Schumann, and G. Tiegs. 2002. Cytokine expression in three mouse models of experimental hepatitis. Cytokine 19: 115–120.CrossRef PubMed
    13.Tsung, A., J.R. Klune, X. Zhang, G. Jeyabalan, Z. Cao, X. Peng, et al. 2007. HMGB1 release induced by liver ischemia involves Toll-like receptor 4 dependent reactive oxygen species production and calcium-mediated signaling. Journal of Experimental Medicine 204: 2913–2923.PubMedCentral CrossRef PubMed
    14.Gong, Q., H. Zhang, J.H. Li, L.H. Duan, S. Zhong, X.L. Kong, et al. 2010. High-mobility group box 1 exacerbates concanavalin A-induced hepatic injury in mice. International Journal of Molecular Medicine (Berl) 88: 1289–1298.CrossRef
    15.Takano, K., M. Shinoda, M. Tanabe, T. Miyasho, S. Yamada, S. Ono, et al. 2010. Protective effect of high-mobility group box 1 blockade on acute liver failure in rats. Shock 34: 573–579.CrossRef PubMed
    16.Zhou, R.R., S.S. Zhao, M.X. Zou, P. Zhang, B.X. Zhang, X.H. Dai, et al. 2011. HMGB1 cytoplasmic translocation in patients with acute liver failure. BMC Gastroenterology 11: 21.PubMedCentral CrossRef PubMed
    17.Tu, C.T., Q.Y. Yao, B.L. Xu, and S.C. Zhang. 2013. Curcumin protects against concanavalin A-induced hepatitis in mice through inhibiting the cytoplasmic translocation and expression of high mobility group box 1. Inflammation 36: 206–215.CrossRef PubMed
    18.Schwabe, R.F., E. Seki, and D.A. Brenner. 2006. Toll-like receptor signaling in the liver. Gastroenterology 130: 1886–1900.CrossRef PubMed
    19.Ojiro, K., H. Ebinuma, N. Nakamoto, K. Wakabayashi, Y. Mikami, Y. Ono, et al. 2010. MyD88-dependent pathway accelerates the liver damage of Concanavalin A-induced hepatitis. Biochemical and Biophysical Research Communications 399: 744–749.CrossRef PubMed
    20.Takeuchi, O., and S. Akira. 2010. Pattern recognition receptors and inflammation. Cell 140: 805–820.CrossRef PubMed
    21.Xu, J., X. Zhang, M. Monestier, N.L. Esmon, and C.T. Esmon. 2011. Extracellular histones are mediators of death through TLR2 and TLR4 in mouse fatal liver injury. Journal of Immunology 187: 2626–2631.CrossRef
    22.Tu, C.T., B. Han, Q.Y. Yao, Y.A. Zhang, H.C. Liu, and S.C. Zhang. 2012. Curcumin attenuates Concanavalin A-induced liver injury in mice by inhibition of toll-like receptor (TLR) 2, TLR4 and TLR9 expression. International Immunopharmacology 12: 151–157.CrossRef PubMed
    23.Formica, J.V., and W. Regelson. 1995. Review of the biology of quercetin and related bioflavonoids. Food and Chemical Toxicology 33: 1061–1080.CrossRef PubMed
    24.Del, P.A., A. Scalera, M.D. Iadevaia, A. Miranda, C. Zulli, L. Gaeta, et al. 2012. Herbal products: benefits, limits, and applications in chronic liver disease. Evidence-based Complementary and Alternative Medicine 2012: 837939.
    25.Bhaskar, S., V. Shalini, and A. Helen. 2011. Quercetin regulates oxidized LDL induced inflammatory changes in human PBMCs by modulating the TLR-NF-kappaB signaling pathway. Immunobiology 216: 367–373.CrossRef PubMed
    26.Marcolin, E., B. San-Miguel, D. Vallejo, J. Tieppo, N. Marroni, J. Gonzalez-Gallego, et al. 2012. Quercetin treatment ameliorates inflammation and fibrosis in mice with nonalcoholic steatohepatitis. Journal of Nutrition 142: 1821–1828.CrossRef PubMed
    27.Byun, E.B., M.S. Yang, H.G. Choi, N.Y. Sung, D.S. Song, S.J. Sin, et al. 2013. Quercetin negatively regulates TLR4 signaling induced by lipopolysaccharide through Tollip expression. Biochemical and Biophysical Research Communications 431: 698–705.CrossRef PubMed
    28.Tang, D., R. Kang, W. Xiao, H. Zhang, M.T. Lotze, H. Wang, et al. 2009. Quercetin prevents LPS-induced high-mobility group box 1 release and proinflammatory function. American Journal of Respiratory Cell and Molecular Biology 41: 651–660.PubMedCentral CrossRef PubMed
    29.Su, J.F., C.J. Guo, J.Y. Wei, J.J. Yang, Y.G. Jiang, and Y.F. Li. 2003. Protection against hepatic ischemia-reperfusion injury in rats by oral pretreatment with quercetin. Biomedical and Environmental Sciences 16: 1–8.PubMed
    30.de David, C., G. Rodrigues, S. Bona, L. Meurer, J. Gonzalez-Gallego, M.J. Tunon, et al. 2011. Role of quercetin in preventing thioacetamide-induced liver injury in rats. Toxicologic Pathology 39: 949–957.CrossRef PubMed
    31.Domitrovic, R., H. Jakovac, M.V. Vasiljev, S. Vladimir-Knezevic, O. Cvijanovic, Z. Tadic, et al. 2012. Differential hepatoprotective mechanisms of rutin and quercetin in CCl (4)-intoxicated BALB/cN mice. Acta Pharmacologica Sinica 33: 1260–1270.PubMedCentral CrossRef PubMed
    32.Yumoto, E., T. Higashi, K. Nouso, H. Nakatsukasa, K. Fujiwara, T. Hanafusa, et al. 2002. Serum gamma-interferon-inducing factor (IL-18) and IL-10 levels in patients with acute hepatitis and fulminant hepatic failure. Journal of Gastroenterology and Hepatology 17: 285–294.CrossRef PubMed
    33.Castellano-Higuera, A., E. Gonzalez-Reimers, M.R. Aleman-Valls, P. Abreu-Gonzalez, F. Santolaria-Fernandez, M.J. De La Vega-Prieto, et al. 2008. Cytokines and lipid peroxidation in alcoholics with chronic hepatitis C virus infection. Alcohol and Alcoholism 43: 137–142.CrossRef PubMed
    34.Zou, Z., B. Li, D. Xu, Z. Zhang, J.M. Zhao, G. Zhou, et al. 2009. Imbalanced intrahepatic cytokine expression of interferon-gamma, tumor necrosis factor-alpha, and interleukin-10 in patients with acute-on-chronic liver failure associated with hepatitis B virus infection. Journal of Clinical Gastroenterology 43: 182–190.CrossRef PubMed
    35.Park, J.S., D. Svetkauskaite, Q. He, J.Y. Kim, D. Strassheim, A. Ishizaka, et al. 2004. Involvement of toll-like receptors 2 and 4 in cellular activation by high mobility group box 1 protein. Journal of Biological Chemistry 279: 7370–7377.CrossRef PubMed
    36.Chen, Y., and R. Sun. 2011. Toll-like receptors in acute liver injury and regeneration. International Immunopharmacology 11: 1433–1441.CrossRef PubMed
    37.Uesugi, T., M. Froh, G.E. Arteel, B.U. Bradford, and R.G. Thurman. 2001. Toll-like receptor 4 is involved in the mechanism of early alcohol-induced liver injury in mice. Hepatology 34: 101–108.CrossRef PubMed
    38.Xiao, X., P. Zhao, D. Rodriguez-Pinto, D. Qi, O. Henegariu, L. Alexopoulou, et al. 2009. Inflammatory regulation by TLR3 in acute hepatitis. Journal of Immunology 183: 3712–3719.CrossRef
    39.Luedde, T., and R.F. Schwabe. 2011. NF-kappaB in the liver—linking injury, fibrosis and hepatocellular carcinoma. Nature Reviews Gastroenterology & Hepatology 8: 108–118.CrossRef
    40.Schumann, J., J. Prockl, A.K. Kiemer, A.M. Vollmar, R. Bang, and G. Tiegs. 2003. Silibinin protects mice from T cell-dependent liver injury. Journal of Hepatology 39: 333–340.CrossRef PubMed
    41.Hoffmann, F., G. Sass, J. Zillies, S. Zahler, G. Tiegs, A. Hartkorn, et al. 2009. A novel technique for selective NF-kappaB inhibition in Kupffer cells: contrary effects in fulminant hepatitis and ischaemia-reperfusion. Gut 58: 1670–1678.CrossRef PubMed
    42.Comalada, M., D. Camuesco, S. Sierra, I. Ballester, J. Xaus, J. Galvez, et al. 2005. In vivo quercitrin anti-inflammatory effect involves release of quercetin, which inhibits inflammation through down-regulation of the NF-kappaB pathway. European Journal of Immunology 35: 584–592.CrossRef PubMed
    43.Bharrhan, S., K. Chopra, S.K. Arora, J.S. Toor, and P. Rishi. 2012. Down-regulation of NF-kappaB signalling by polyphenolic compounds prevents endotoxin-induced liver injury in a rat model. Innate Immunity 18: 70–79.CrossRef PubMed
    44.Liu, H., C.R. Lo, and M.J. Czaja. 2002. NF-kappaB inhibition sensitizes hepatocytes to TNF-induced apoptosis through a sustained activation of JNK and c-Jun. Hepatology 35: 772–778.CrossRef PubMed
  • 作者单位:Xi Li (1) (2)
    Hong-chun Liu (1) (3)
    Qun-yan Yao (1) (3)
    Bei-li Xu (1) (3)
    Shun-cai Zhang (1) (3)
    Chuan-tao Tu (1) (3)

    1. Department of Gastroenterology and Hepatology, Zhongshan Hospital, Fudan University, Shanghai, China
    2. Department of Geriatrics, Zhongshan Hospital, Fudan University, Shanghai, China
    3. Shanghai Institute of Liver Diseases, 180 Fenglin Road, Shanghai, 200032, China
  • 刊物类别:Medicine
  • 刊物主题:Medicine & Public Health
    Rheumatology
    Internal Medicine
    Pharmacology and Toxicology
    Pathology
  • 出版者:Springer Netherlands
  • ISSN:1573-2576
文摘
The dietary flavonoid quercetin has hepatoprotective effects. We analyzed the effects of quercetin on concanavalin A (ConA)-induced hepatitis in mice and its underlying molecular mechanisms of action. Mice were administered quercetin (50 mg/kg body weight, i.p.) or vehicle 30 min before intravenous administration of ConA. Quercetin pretreatment significantly reduced the ConA-induced elevations in plasma aminotransferase concentrations and liver necrosis, as well as reducing serum concentrations of the pro-inflammatory cytokines tumor necrosis factor (TNF)-α, interferon-γ, and interleukin-4. Quercetin pretreatment also reduced expression of high-mobility group box 1 protein (HMGB1) and toll-like receptor (TLR)-2 and TLR-4 messenger RNA (mRNA) and protein in liver tissues. Quercetin pretreatment significantly inhibited degradation of inhibitory kappa B alpha and modulated ConA-induced nuclear translocation in the liver of nuclear factor kappa B (NF-κB) p65. These results demonstrate that quercetin protects against ConA-mediated hepatitis in mice by attenuating the HMGB1–TLRs–NF-κB signaling pathway. KEY WORDS quercetin hepatitis inflammation nuclear factor κB high-mobility group box 1 protein toll-like receptor

© 2004-2018 中国地质图书馆版权所有 京ICP备05064691号 京公网安备11010802017129号

地址:北京市海淀区学院路29号 邮编:100083

电话:办公室:(+86 10)66554848;文献借阅、咨询服务、科技查新:66554700