Resolvin D1 attenuates lipopolysaccharide induced acute lung injury through CXCL-12/CXCR4 pathway

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• 作者：Wang Yaxin ; MD¹ ; Yao Shanglong ; MD ; PhD¹ ; Shu Huaqing ; MD ; PhD ; ^{huaqingshu_2005@hotmail.com" class="auth_mail} ; Liu Hong ; MD ; Yuan Shiying ; MD ; PhD ; Chen Xiangdong ; MD ; PhD ; Li Ruidong ; MD ; Wu Xiaoying ; MD ; Guo Lina ; MD ; Wang Yan ; MD
• 关键词：Acute lung injury ; Inflammation ; Neutrophil ; Resolvin D1
• 刊名：Journal of Surgical Research
• 出版年：1 May, 2014
• 年：2014
• 卷：188
• 期：1
• 页码：213-221
• 全文大小：2699 K

文摘

Background

The recruitment of neutrophils plays an important role in the progress of acute lung injury (ALI). Excessive neutrophils released from bone marrow accumulate in lung, release proinflammatory factors, and cause tissue damage. CXCL-12/CXCR4 is an important signaling pathway, which regulates the migration of bone marrow hematopoietic cells out of bone marrow and involves in neutrophil accumulation and retention in the inflammatory site. Resolvin D1 (RvD1) is a kind of lipid mediators, which can alleviate many inflammatory diseases. We hypothesized that RvD1 can alleviate lipopolysaccharide (LPS)-induced ALI through regulating CXCL-12/CXCR4 pathway.

Methods

We randomized mice into five groups: control group, RvD1 group, LPS group, LPS plus RvD1 group, and LPS plus AMD3100 group. ALI was established by intratracheal instillation of LPS. After 24 and 72聽h, mice were sacrificed, and lung tissues were harvested for histologic analysis, wet-to-dry ratio, myeloperoxidase activity, and CXCL-12 expression. Bronchoalveolar fluid was collected for protein analysis, cytokines assay, and flow cytometry analysis.

Results

Histologic findings as well as wet-to-dry ratio, protein concentration, cytokines assay, neutrophil number, and myeloperoxidase activity confirmed that RvD1 and AMD3100 alleviated LPS-induced ALI. RvD1 decreased CXCL-12 messenger RNA expression in lung. However, RvD1 promoted CXCR4 expression in neutrophils in the initial stage of inflammation and reduced its level in the later stage.

Conclusions

RvD1 protects LPS-induced ALI partially through regulating CXCL-12/CXCR4 pathway.