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Protective effects of IL-4 on Bacillus Calmette-Guerin and lipopolysaccharide induced immunological liver injury in mice

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Abstract

Objective

Mice injected with Bacillus Calmette-Guérin (BCG) were challenged with lipopolysaccharide (LPS) to induce inflammatory liver injury. This study was performed to explore the protective effects of interleukin (IL)-4 against liver injury induced by BCG and LPS in mice.

Materials and methods

Mice injected with BCG (125 mg/kg) were challenged with LPS (10 μg/kg) to induce the model of inflammatory liver injury. Half an hour after injection of LPS, mice were subcutaneously administered rmIL-4 at 5 and 0.5 μg/kg, respectively. Liver injury was evaluated by serum transaminase assay and H & E staining. Liver cytokine concentrations were determined by enzyme-linked immunosorbent assay, and intrahepatic cytokine and iNOS mRNA levels by reverse transcriptase polymerase chain reaction. Intrahepatic apoptosis was evaluated by terminal deoxynucleotidyl transferase mediated nick end labeling. NF-κB p65 and ERK signal pathway was detected by Western-blotting. NF-κB signal pathway was also detected by electrophoretic mobility shift assay.

Results

IL-4 reduced the serum ALT, AST and LDH, alleviated the inflammatory cells infiltration, down regulated the expression of TNF-α, IL-1β, IFN-γ, IL-6 and iNOS mRNA in liver, and alleviated hepatic glutathione depletion (GSH). In addition, IL-4 displayed inhibition of extracellular signal-regulated kinase phosphorylation and NF-κB activation.

Conclusion

IL-4 may protect mice against BCG/LPS-induced immune liver injury, besides ERK and NF-κB signal pathways were involved in the effects.

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Acknowledgments

This work was supported by National Science and Technology Key Projects on “Major Infectious Diseases such as HIV/AIDS, Viral Hepatitis Prevention and Treatment” (2008ZX10002-009). The authors thank Shijiazhuang Pharmaceutical Group Company for their contribution to this work.

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Authors and Affiliations

  1. State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China

    Nan N. Zhang, Nong Y. Huang, Xi K. Zhou, Xiao L. Luo, Ji Qiu, Yin B. Zhang, Xiu Teng & Can Luo

  2. State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, 1# Keyuan Road 4, Gaopeng Street, High Technological Development Zone, Chengdu, 610041, China

    Yan Zhang, Xian C. Chen, Bing Kan, Yong Q. Mao, Ai P. Tong, Yu Q. Wei & Jiong Li

  3. State Key Laboratory of Biotherapy, West China Hospital, and School of Life Science, Sichuan University, Chengdu, China

    Chang Y. Liu

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Correspondence to Jiong Li.

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Responsible Editor: Liwu Li.

N. N. Zhang, N. Y. Huang are contributed equally to this work.

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Zhang, N.N., Huang, N.Y., Zhou, X.K. et al. Protective effects of IL-4 on Bacillus Calmette-Guerin and lipopolysaccharide induced immunological liver injury in mice. Inflamm. Res. 61, 17–26 (2012). https://doi.org/10.1007/s00011-011-0383-9

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  • DOI: https://doi.org/10.1007/s00011-011-0383-9

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