Li Liangzi, Zhou Chao, Li Teming, Xiao Weidong, Yu Min, Yang Hua
Department of General Surgery, Xinqiao Hospital, Army Medical University, Chongqing, China.
Ann Transl Med. 2021 Mar;9(5):365. doi: 10.21037/atm-20-5494.
Interleukin-28A (IL-28A or interferon-λ2) is reported to maintain intestinal mucosal homeostasis. However, the effects and mechanisms of IL-28A on intestinal ischemia reperfusion (I/R) have not yet been studied.
Adult C57BL/6 mice were randomly divided into three groups: sham, I/R, and I/R+IL-28A (n=5 in each group). The I/R+IL-28A group mice were injected with recombinant mouse IL-28A 12 hours before the operation. Mice were sacrificed 6 hours after reperfusion. The mucosal permeability was investigated, and histology analyses were performed. Additionally, a hypoxic Caco-2 cell culture model was established. Fludarabine was used to inhibit phosphorylated signal transducer and activator of transcription 1 (pSTAT1). The expression of IL-28A, tight junctions (TJs), and pSTAT1 was assessed by western blot, immunohistochemical (IHC) staining, or immunofluorescence staining. Epithelial permeability was measured by transepithelial electrical resistance (TER).
The expression of IL-28A was decreased in intestinal lamina propria in the I/R group compared with the control group. Administration of IL-28A significantly alleviated the I/R-induced increase in intestinal permeability and tissue damage. Treatment with IL-28A significantly attenuated intestinal I/R-induced disruption of TJ proteins, including zonula occludens-1 (ZO-1), occludin, and claudin-1. , IL-28A treatment reversed the decrease in TER of Caco-2 monolayers exposed to hypoxic environments. IL-28A led to the activation of STAT1 and the upregulation of claudin-1 expression both and . Also, inhibiting phosphorylation of STAT1 reversed the effects of IL-28A on the expression and distribution of claudin-1 in Caco-2 cells.
Intestinal epithelial barrier dysfunction caused by intestinal I/R is ameliorated by IL-28A via the regulation of claudin-1.
据报道，白细胞介素-28A（IL-28A或干扰素-λ2）可维持肠道黏膜稳态。然而，IL-28A对肠道缺血再灌注（I/R）的影响及机制尚未得到研究。
将成年C57BL/6小鼠随机分为三组：假手术组、I/R组和I/R+IL-28A组（每组n = 5）。I/R+IL-28A组小鼠在手术前12小时注射重组小鼠IL-28A。再灌注6小时后处死小鼠。检测黏膜通透性，并进行组织学分析。此外，建立缺氧的Caco-2细胞培养模型。使用氟达拉滨抑制磷酸化信号转导和转录激活因子1（pSTAT1）。通过蛋白质免疫印迹法、免疫组织化学（IHC）染色或免疫荧光染色评估IL-28A、紧密连接（TJ）和pSTAT1的表达。通过跨上皮电阻（TER）测量上皮通透性。
与对照组相比，I/R组小鼠肠固有层中IL-28A的表达降低。给予IL-28A可显著减轻I/R诱导的肠道通透性增加和组织损伤。IL-28A治疗可显著减轻肠道I/R诱导的TJ蛋白破坏，包括闭合蛋白-1（ZO-1）、封闭蛋白和claudin-1。IL-28A治疗可逆转暴露于缺氧环境的Caco-2单层细胞TER的降低。IL-28A导致STAT1激活以及claudin-1表达上调。此外，抑制STAT1磷酸化可逆转IL-28A对Caco-2细胞中claudin-1表达和分布的影响。
IL-28A通过调节claudin-1改善肠道I/R引起的肠上皮屏障功能障碍。
