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miR-199b-5p Regulates Immune-Mediated Allograft Rejection after Lung Transplantation Through the GSK3β and NF-κB Pathways

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Abstract

Emerging evidence indicates that acute rejection mainly associated with the inflammatory response is an independent risk factor for chronic rejection after lung transplantation. Monocytes are the main pro-inflammatory leukocytes infiltrating around the lesions and play vital roles in triggering the acute rejection. In the rat lung transplantation model, lipopolysaccharide (LPS)-induced severe acute rejection was strongly associated with advanced chronic rejection. The exact regulatory mechanism of pro-inflammation in monocytes is not yet clear. In this study, we identified a novel anti-inflammatory effect of miR-199b-5p (miR-199b) through the GSK3β and NF-κB pathways. THP-1 monocytes treated with LPS showed a significant decrease in miR-199b that is inversely correlated to GSK3β expression and NF-κB activation. Furthermore, the NF-κB-associated inflammatory response was reduced due to the overexpression of miR-199b targeting GSK3β, which was rescued by the inhibition of miR-199b. These results indicated that miR-199b attenuated the inflammatory response at least partly through the GSK3β/NF-κB signaling pathways in monocytes. Our data point toward a potentially important role for miR-199b in the inhibition of rejection after lung transplantation.

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Funding

This study was supported by the National Natural Science Foundation of China (Project 81373161) and two awards from the Health Department of Zhejiang Province, China (Project 2012ZDA017, 2012KYA081).

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Authors and Affiliations

  1. Department of Thoracic Surgery, the First Affiliated Hospital, School of Medicine, Zhejiang University, No. 79 Qingchun Road, Hangzhou, 310003, China

    Linhai Zhu, Haichao Xu, Wang Lv, Zhehao He, Peng Ye, Yiqing Wang & Jian Hu

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  1. Linhai Zhu
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  2. Haichao Xu
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Correspondence to Jian Hu.

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Zhu, L., Xu, H., Lv, W. et al. miR-199b-5p Regulates Immune-Mediated Allograft Rejection after Lung Transplantation Through the GSK3β and NF-κB Pathways. Inflammation 41, 1524–1535 (2018). https://doi.org/10.1007/s10753-018-0799-2

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