Department of Thoracic Surgery, the First Affiliated Hospital, School of Medicine, Zhejiang University, No. 79 Qingchun Road, Hangzhou, 310003, China.
Inflammation. 2018 Aug;41(4):1524-1535. doi: 10.1007/s10753-018-0799-2.
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.
新出现的证据表明，急性排斥反应主要与炎症反应有关，是肺移植后慢性排斥反应的独立危险因素。单核细胞是浸润在病变周围的主要促炎白细胞，在触发急性排斥反应中起着至关重要的作用。在大鼠肺移植模型中，脂多糖（LPS）诱导的严重急性排斥反应与晚期慢性排斥反应强烈相关。单核细胞中促炎的精确调节机制尚不清楚。在这项研究中，我们通过 GSK3β 和 NF-κB 通路发现了 miR-199b-5p（miR-199b）的一种新的抗炎作用。用 LPS 处理的 THP-1 单核细胞中 miR-199b 显著减少，与 GSK3β 表达和 NF-κB 激活呈负相关。此外，由于靶向 GSK3β 的 miR-199b 的过表达，NF-κB 相关的炎症反应减少，这可以通过抑制 miR-199b 得到挽救。这些结果表明，miR-199b 通过 GSK3β/NF-κB 信号通路至少部分减轻了单核细胞中的炎症反应。我们的数据表明，miR-199b 在肺移植后抑制排斥反应方面可能具有重要作用。
