Background: NF-κB plays a key role in ischemia reperfusion injury (IRI). Systemic inhibition of NF-κB by various methods has been proven to ameliorate IRI. However, NF-κB is also responsible for tissue protection against IRI. Systemic NF-κB inhibition may not be the optimal way for preventing IRI because of its complex roles. T cells are essential in mediating IRI. NF-κB is an important molecule during T cell activation. It is not clear the effect of T cell–specific NF-κB inhibition on IRI. We aimed to study the effect of T cell–specific NF-κB inhibition on renal IRI in IκBαΔN-Tg mice. We also compared the different effects between T cell–specific and systemic NF-κB inhibition on IRI.
Methods: Renal IRI was induced by left renal pedicle clamping for 60 or 80 min in wild-type, ursolic acid–treated or IκBαΔN-Tg mice. Renal function, histologic examination and overall survival after lethal IRI was evaluated in each group.
Results: Serum creatinine, BUN, and pathologic damage were all reduced in IκBαDN-Tg mice and ursolic acid–treated mice than those in the control group. All the above indexes were improved better in IκBαDN-Tg mice than those in ursolic acid–treated mice. The survival rate of IκBαDN-Tg mice was higher than that of ursolic acid–treated mice after lethal kidney ischemia reperfusion injury. Immunohistochemistry showed a significant reduced CD4+ T cells and neutrophil infiltration in IκBαDN-Tg mice.
Conclusion: T cell–specific NF-κB inhibition provides powerful protective effect against renal IRI.
1 Institute of Organ Transplantation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; Key Laboratory of Ministry of Health, and Key Laboratory of Ministry of Education, China.
2 Department of Anesthesiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
3 Address correspondence to: Ping Zhou, 1095 Jiefang Road, Tongji Hospital, Institute of Organ Transplantation, Wuhan, Hubei 430030, China.
Ping Zhou and Yong Liu were supported by the National Natural Science Foundation of China (Grant Nos. 30772041 and 81373168, respectively).
The authors declare no conflicts of interest.
C.X. participated in research design, the performance of the research and the writing of the paper. Y.L. participated in research design and the writing of the paper. C.L., Y.L., and T.Y. participated in the performance of the research. L.X. participated in revising the paper. P.Z. participated in research design and revising the paper. C.B.X. and Y.L. contributed equally to this work.
Received 12 July 2013. Revision requested 31 July 2013.
Accepted 04 November 2013.
Accepted January 7, 2014