IL35 通过调节巨噬细胞极化来减轻 LPS 诱导的急性肺损伤。
IL35 attenuated LPS-induced acute lung injury by regulating macrophage polarization.
机构信息
Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, China-Japan Friendship Hospital, No 2, East Yinghua Road, Chaoyang District, 100029, Beijing, P. R. China.
Graduate School of Peking Union Medical College, Chinese Academy of Medical Sciences, No 9, Dongdan Santao, Dongcheng District, 100730, Beijing, P. R. China.
出版信息
Mol Biol Rep. 2022 Jul;49(7):5811-5820. doi: 10.1007/s11033-022-07293-5. Epub 2022 Jun 24.
BACKGROUND
Interleukin 35 (IL35) has been reported to play a role in acute lung injury (ALI); however, the current results regarding the relationship between IL35 and ALI are inconsistent. Therefore, we aimed to further determine the function of IL35 in ALI in mice and the potential mechanism in this paper.
MATERIALS AND METHODS
Hematoxylin-eosin (HE) staining and Masson staining were used to evaluate lung injury in mice. Immunohistochemical staining was used to evaluate the expression of IL35 p35, TLR4 and MD2 and the Bax/Bcl2 and p-P65/P65 ratios. The expression levels of IL35 EBi3, CD68, CD206 and MPO were assessed by immunofluorescence staining. RT-PCR was used to examine the expression levels of IL1β and IL6. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining was performed to detect apoptotic cells.
RESULTS
Overexpression of IL35 alleviated LPS-induced ALI in mice. IL35 overexpression decreased the expression of CD68 and increased the expression of CD206 in mice with ALI. Furthermore, upregulation of IL35 expression obviously reduced the expression of MPO, IL1β and IL6 in the lung tissues of mice with ALI. Mechanistically, IL35 suppressed the TLR4/NFκB-P65 pathway, leading to the promotion of the M1 to M2 macrophage transition and alleviation of inflammation in mice with ALI.
CONCLUSIONS
IL35 relieved LPS-induced inflammation and ALI in mice by regulating M1/M2 macrophage polarization and inhibiting the activation of the TLR4/NFκB-P65 pathway.
背景
白细胞介素 35（IL-35）已被报道在急性肺损伤（ALI）中发挥作用；然而，目前关于 IL-35 与 ALI 之间关系的结果并不一致。因此，我们旨在进一步确定 IL-35 在小鼠 ALI 中的功能及其潜在机制。
材料和方法
苏木精-伊红（HE）染色和 Masson 染色用于评估小鼠的肺损伤。免疫组织化学染色用于评估 IL-35 p35、TLR4 和 MD2 的表达以及 Bax/Bcl2 和 p-P65/P65 比值。免疫荧光染色用于评估 IL-35 EBi3、CD68、CD206 和 MPO 的表达水平。RT-PCR 用于检测 IL1β 和 IL6 的表达水平。末端脱氧核苷酸转移酶介导的 dUTP 缺口末端标记（TUNEL）染色用于检测凋亡细胞。
结果
过表达 IL-35 减轻 LPS 诱导的小鼠 ALI。IL-35 过表达降低了 ALI 小鼠中 CD68 的表达并增加了 CD206 的表达。此外，IL-35 表达的上调明显降低了 ALI 小鼠肺组织中 MPO、IL1β 和 IL6 的表达。机制上，IL-35 抑制了 TLR4/NFκB-P65 通路，导致 M1 向 M2 巨噬细胞转化的促进和 ALI 小鼠炎症的减轻。
结论
IL-35 通过调节 M1/M2 巨噬细胞极化和抑制 TLR4/NFκB-P65 通路的激活，缓解 LPS 诱导的小鼠炎症和 ALI。
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