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Anti-IL-23 exerted protective effects on cerebral ischemia–reperfusion injury through JAK2/STAT3 signaling pathway

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Abstract

Ischemia–reperfusion frequently occurs in ischemic cerebral vascular disease, during which the inflammatory signaling plays essential roles. The aim of this study was to discover the efficacy of the antibody to a key immune cytokine IL-23 (anti-IL-23) for the therapy of cerebral ischemia–reperfusion injury. We established the cerebral ischemia–reperfusion injury model by middle cerebral artery occlusion (MCAO). Anti-IL-23 injection attenuated lesions indicated by histology study. RT-PCR and Western blot were employed to detect the mRNA and protein expression of JAK2 and STAT3 after anti-IL-23 treatment. ELISA was utilized to measure the levels of MDA (malondialdehyde) and superoxide dismutase (SOD). Moreover, curcumin and IL-6 were implicated in the endogenous intervention of IL-23 signaling in vivo. Our data demonstrated that the treatment of anti-IL-23 might transcriptionally activate the classic immune pathway in the brain. Anti-IL-23 augmented phosphorylation levels of both JAK2 and STAT3, suggesting the amplification signaling of JAK/STAT after exogenous IL-23 intervention. Anti-IL-23 reduced ROS molecules of STAT downstream in the serum and brain. It also alleviated the injury by bringing down levels of MDA and SOD in the serum. JAK2 inhibitor could abolish the effect of anti-IL-23 whereas JAK3 ameliorated the injury. The combination of anti-IL-23 and JAK3i could reduce infarct volume more effectively. In summary, this study indicated that anti-IL-23 had protective effects against cerebral ischemia–reperfusion injury by targeting the immune specific JAK2-STAT3 in JAK/STAT pathway.

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The authors confirm that all data underlying the findings are fully available without restriction. All relevant data are within the paper and its supporting information files.

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Acknowledgements

The authors would like to thank Beijing Chaoyang Hospital, Capital Medical University for their technical assistance.

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Authors and Affiliations

  1. Department of Neurology, Beijing Chaoyang Hospital, Capital Medical University, No. 5 Jingyuan Road, Shijingshan District, Beijing, 100043, China

    Lichao Fan & Lichun Zhou

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  1. Lichao Fan
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  2. Lichun Zhou
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LF and LZ designed the study, performed the research, analysed data, and wrote the paper.

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Correspondence to Lichun Zhou.

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The authors declare no conflict of interest.

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This study was approved by animal use committee of Beijing Chaoyang Hospital, Capital Medical University and conducted in strict accordance with the national institutes of health guidelines for the care and use of experimental animals.

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Fan, L., Zhou, L. Anti-IL-23 exerted protective effects on cerebral ischemia–reperfusion injury through JAK2/STAT3 signaling pathway. Mol Biol Rep 48, 3475–3484 (2021). https://doi.org/10.1007/s11033-021-06339-4

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  • DOI: https://doi.org/10.1007/s11033-021-06339-4

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