Characteristics of Changes in Inflammatory Cytokines as a Function of Hepatic Ischemia-Reperfusion Injury Stage in Mice
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Liver ischemia-reperfusion injury (IRI) can severely compromise the prognosis of patients receiving liver surgery. While inflammation contributes to the damage resulting from IRI, only a limited number of inflammation biomarkers have been identified as being associated with the different stages of hepatic IRI. As an approach to identify some of these inflammatory cytokines and the molecular mechanisms involved within different stages of hepatic IRI, we used an advanced antibody array assay to detect multiple proteins. With this technology, we observed specific differences in the content of inflammatory cytokines between ischemic and sham controls, as well as a function of the different reperfusion stages in a hepatic IRI mouse model. For example, while liver tissue content of IL-12p40/p70 was significantly increased in the ischemic stage, it was significantly decreased in the reperfusion stage as compared with that of the sham group. For other inflammatory cytokines, no changes were obtained between the ischemic and reperfusion stages with levels of IL-17, Eotaxin-2, Eotaxin, and sTNF RII all being consistently increased, while those of TIMP-1, TIMP-2, BLC, and MCSF consistently decreased as compared with that of the sham group at all reperfusion stages examined. Results from protein function annotation Gene Ontology and the KEGG pathway revealed that inflammatory cytokines are enriched in a network associated with activation of inflammatory response signaling pathways such as TLR, TNF, and IL-17 when comparing responses of the IR versus sham groups. The identification of cytokines along with their roles at specific stages of IRI may reveal important new biological markers for the diagnosis and prognosis of hepatic IRI.
KEY WORDShepatic ischemia-reperfusion injury inflammatory cytokines diagnosis and prognosis biomarker
All the authors would like to thank the members of the Research Center of Medical College of Henan Polytechnic University, and Life Science Research Center of the First Affiliated Hospital of Xinxiang Medical University for their technical support.
Li SP, Wang FF, and Zhang WK performed the majority of experiments and analyzed the data; Bian MZ and Zhang SY performed the molecular investigations; Li SP, Fang Y, Yan H, and Zhang WK participated equally in treatment of animals; Li SP and Zhang HM designed and coordinated the research; Li SP wrote the paper.
This work was supported by National Natural Science Foundation of China (No. 81700556).
Compliance with Ethical Standards
Conflict of Interest
The authors declare that they have no conflict of interest.
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