Dynamic variation of inflam matory cytokines,chemokines and Toll-like receptors in APAP-induced liver injury

Abstract

Abstract: Objective To explore the dynamic changes ofinflam matory cytokines,chem okines and Toll-like receptors （TLR）in acetaminophen（APAP）-induced liver injury within 24 hours. Methods C57BL/6 mice were rando mly divided into six groups：control group,APAP1h group,APAP3h group,APAP6h group,APAP12h group and APAP24h group,including 5 mice in each group. After fasting for 15 hours,control group were given 0.9％saline by intraperitoneal injection,w hile other groups were given 300 Mg/kg APAP. Assessment of the various inflam matory cytokines,chem okines and TLRin mice liver was carried out at MRNAlevel by realtime poly merase chain reaction（RT-PCR）. Degrees of APAP-induced liver injury were evaluated by haematoxylin eosin（HE）staining. Results According to HEstaining result,APAP-induced liver injury in APAPgroups increasingly aggravated within 24 hours w hen compared with that in control group.In APAPgroups,RT-PCRindicated that MRNAlevels of IL-6,IL-10,IL-1βand IP-10 rose to various degrees at different time points,w hile MIP-3α MRNAlevels declined distinctly（P<0.05）,which was in contrast to control group. Additionally,variation ofinterferon（IFN）-γ and tu Mor necrosis factor（TNF）-α had no statistical difference between APAPand control groups.In APAPgroups,levels of CXCR-2 and CCR-2 were obviously lower at 24h（P<0.05）than those in control group,w hile level of CXCL-2 rose to 14.8 and 7.8 times higher at 12h and 24h（P<0.05）,respectively. Furtherm ore,levels of TLR-9 and TLR-4 changed to various extents at different time points（P<0.05）. Conclusion APAPfor 300 Mg/kg induces mice liver injury within 24h,which makes inflam matory cytokines,chem okines and TLRchange obviously at MRNAlevels in mice liver.

Key words: Acetaminophen, Cytokine, Chem okine, Toll-like receptor

JIN Yu-ting, LI Da-wei, MING Ya-nan, ZHANG Jiang, ZHANG Ming, XIA Qiang. Dynamic variation of inflam matory cytokines,chemokines and Toll-like receptors in APAP-induced liver injury[J]. Chinese Hepatolgy, 2016, 21(1): 24-27.

References

1 Cooper SC,Aldridge RC,Shah T,et al.Outcomes of liver transplantation for paraceta Mol(aceta minophen)-induced hepatic failure. Liver Transpl,2009,15:1351-1357.
2 Ren SG,Malozowski S,Sanchez P,et al.Direct ad ministration of testosterone increases rat tibial epiphyseal growth plate width. Acta Endocrinol,1989,121:401-405.
3 Mitchell JR,Jollow DJ,Potter WZ,et al.Aceta minophen-induced hepatic necrosis. I. Role of drug metabolism. JPharmacol Exp Ther,1973,187:185-194.
4 Saini SP,Zhang B,Niu Y,et al.Activation of liver Xreceptor increases aceta minophen clearance and prevents its toxicity in mice. Hepatology,2011,54:2208-2217.
5 Jaeschke H.Role ofinflam mation in the mechanism of acetaminopheninduced hepatotoxicity. Expert Opin Drug Metab Toxicol,2005,1:389-397.
6 Laskin DL,Pilaro AM,Ji S.Potentialrole of activated macrophagesin aceta minophen hepatotoxicity. II. Mechanism of macrophage accu Mulation and activation. Toxicol Appl Pharmacol,1986,86:216-226.
7 Ishida Y,Kondo T,Ohshima T,et al.Apivotal involvement of IFN-ga Mma in the pathogenesis of aceta minophen-induced acute liver injury. FASEBJ,2002,16:1227-1236.
8 Masubuchi Y,Bourdi M,Reilly TP,et al.Role ofinterleukin-6 in hepatic heat shock protein expression and protection against aceta minophen-induced liver disease. Biochem Biophys Res comMun,2003,304:207-212.
9 Bourdi M,Masubuchi Y,Reilly TP,et al.Protection against aceta minophen-induced liver injury and lethality by interleukin 10:role of inducible nitric oxide synthase. Hepatology,2002,35:289-298.
10 Gardner CR,Laskin JD,Dambach DM,et al.Exaggerated hepatotoxicity of aceta minophen in mice lacking tu Mor necrosis factor receptor-1. Potential role of infla Mmatory mediators. Toxicol Appl Pharmacol,2003,192:119-130.
11 Bone-Larson CL,Hogaboam CM,Evanhoff H,et al.IFN-gam mainducible protein-10(CXCL10)is hepatoprotective during acute liver injury through the induction of CXCR2 on hepatocytes. JIm Munol,2001,167:7077-7083.
12 Hogaboam CM,Bone-Larson CL,Steinhauser ML,et al.Exaggerated hepatic injury due to aceta minophen challenge in mice lacking C-Cchem okine receptor 2. AMJpathol,2000,156:1245-1252.

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