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Kupffer cells contribute to concanavalin A-induced hepatic injury through a Th1 but not Th17 type response-dependent pathway in mice |
Lin Chen, Xiao-Jun Xie, Yu-Fu Ye, Lin Zhou, Hai-Yang Xie, Qin-Fen Xie, Jiong Tian and Shu-Sen Zheng |
Hangzhou, China
Author Affiliations: Zhejiang University School of Medicine, Hangzhou 310003, China (Chen L, Xie XJ and Ye YF); Key Laboratory of Combined Multi-organ Transplantation, Ministry of Public Health; Department of Hepatobiliary and Pancreatic Surgery (Zhou L, Xie HY, Xie QF and Zheng SS), Department of Nephrology (Tian J), First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China
Corresponding Author: Shu-Sen Zheng, MD, PhD, Key Laboratory of Combined Multi-organ Transplantation, Ministry of Public Health, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China (Tel: 86-571-87236570; Fax: 86-571-87236466; Email: shusenzheng@zju.edu.cn) |
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Abstract BACKGROUND: Increasing evidence suggests that a close interaction of Kupffer cells with T cells plays a central role in concanavalin A-induced hepatic injury in mice, but the underlying mechanisms remain obscure. The present study aimed to determine the relative roles of Th1 and Th17 type responses in concanavalin A-induced hepatic injury in mice, and to investigate whether or not Kupffer cells contribute to hepatic injury via a Th1 or Th17 type response-dependent pathway.
METHODS: Immune-mediated hepatic injury was induced in C57BL/6 mice by intravenous injection of concanavalin A. Kupffer cells were inactivated by pretreatment with gadolinium chloride 24 hours before the concanavalin A injection. The interferon-gamma (IFN-γ) and interleukin-17 (IL-17) pathways were blocked by specific neutralizing antibodies. Hepatic injury was assessed using serum transferase activity and pathological analysis. Expression of inflammatory cytokines within the liver was detected by real-time polymerase chain reaction and immunohistochemistry.
RESULTS: Neutralization of IFN-γ significantly attenuated concanavalin A-induced hepatic injury. However, neutralization of IL-17 failed to suppress the injury. Inactivation of Kupffer cells by gadolinium chloride pretreatment protected against concanavalin A-induced injury and significantly reduced hepatic cytokine levels including TNF-α, IL-6 and IFN-γ but not IL-17.
CONCLUSION: Our findings suggest that Kupffer cells contribute to concanavalin A-induced hepatic injury via a Th1 type response-dependent pathway and production of inflammatory cytokines including TNF-α, IL-6 and IFN-γ.
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Cite this article: |
Chen L,
Xie XJ,
Ye YF,
et al.
Kupffer cells contribute to concanavalin A-induced hepatic injury through a Th1 but not Th17 type response-dependent pathway in mice.
Hepatobiliary Pancreat Dis Int
2011;
10(2):
171-178. DOI:
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URL: |
http://dx.doi.org/ OR http://www.hbpdint.com/EN/Y2011/V10/I2/171 |
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