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Lack of SOCS3 increases LPS-induced murine acute lung injury through modulation of Ly6C(+) macrophages 期刊论文

编号：

0192926b-9b41-4b6a-9c72-e089a3bdf086
作者：

Jiang, Zhilong(姜志龙)#^[1]Chen, Zhihong(陈智鸿)^[1]Li, Liyang^[1];Zhou, Wenjun^[1];Zhu, Lei(朱蕾)*^[1]
语种：

English
期刊：

RESPIRATORY RESEARCH ISSN：1465-993X 2017 年 18 卷 ; DEC 29
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关键词：

Acute lung injury Ly6C(+) macrophages SOCS3 JAK/STAT3 signaling
摘要：

Background: SOCS3 (suppressor of cytokine signaling 3) is a negative regulator of JAK/STAT3 signaling pathway and participates in the regulation of lung inflammation in a mouse model with acute lung injury (ALI). However, it is not well understood how SOCS3 regulates lung inflammation in the ALI mouse model. Method: In the present study, we investigated the effects of SOCS3 on modulation of Ly6C(+) monocyte phenotypes in a mouse model with lipopolysaccharide (LPS)-induced ALI. Conditional SOCS3(Lyz2cre) mice with myeloid cell-restricted depletion of SOCS3 gene were created by breeding transgenic Lyz2Cre mice with SOCS3(fl/fl) mice. Wilde-type (WT) and SOCS3(Lyz2cre) mice were intratracheal instilled with 5 mg/kg LPS for 2 days. Lung, bronchoalveolar lavage (BAL) and blood were collected for analysis by flow cytometry, ELISA, qRT-PCR and Western blot analysis. Results: The studies in the ALI mouse model revealed that myeloid cell-restricted SOCS3 deficiency exacerbated the severity of ALI as compared to the WT mice. The increased severity of ALI in SOCS3-deficient mice was associated with higher populations of neutrophils, T lymphocytes and Ly6C(+) monocytes in the inflamed lung tissues. In addition, CCR2 and CXCL15 were elevated, and accompanied by greater expression and activation of STAT3 in the lung of SOCS3-deficient mice. SOCS3-deficient bone marrow-derived macrophages (BMDMs) expressed a higher amount of TNF-alpha, and adoptive transfer of the SOCS3-deficient Ly6C(+) BMDMs into WT mice enhanced the severity of ALI than adoptive transfer of WT control BMDMs. However, depletion of Ly6C(+) circulating monocytes by anti-Ly6C(+) neutralizing antibody moderately attenuated neutrophil infiltration and resulted in lower prevalence of Ly6C(+) cells in the lung of treated mice. Conclusion: Myeloid cell-restricted lack of SOCS3 induced more severe ALI through modulation of Ly6C(+) subtype macrophages. The results provide insight into a new role of SOCS3 in modulation of Ly6C(+) monocyte phenotypes and provide a novel therapeutic strategy for ALI by molecular intervention of macrophages subtypes.
推荐引用方式
GB/T 7714：

Jiang Zhilong,Chen Zhihong,Li Liyang, et al. Lack of SOCS3 increases LPS-induced murine acute lung injury through modulation of Ly6C(+) macrophages [J].RESPIRATORY RESEARCH,2017,18.
APA：

Jiang Zhilong,Chen Zhihong,Li Liyang,Zhou Wenjun,&Zhu Lei.(2017).Lack of SOCS3 increases LPS-induced murine acute lung injury through modulation of Ly6C(+) macrophages .RESPIRATORY RESEARCH,18.
MLA：

Jiang Zhilong, et al. "Lack of SOCS3 increases LPS-induced murine acute lung injury through modulation of Ly6C(+) macrophages" .RESPIRATORY RESEARCH 18(2017).

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