Resolution of PMA-Induced Skin Inflammation Involves Interaction of IFN-γ and ALOX15

被引:27
作者
Zhang, Guojun [1 ]
Liu, Xiaoman [2 ]
Wang, Chunhui [2 ,3 ]
Qu, Liwei [2 ,3 ]
Deng, Jingjing [2 ,3 ]
Wang, Hui [1 ]
Qin, Zhihai [2 ]
机构
[1] Xinxiang Med Univ, Immunol Res Ctr, Xinxiang 453003, Henan, Peoples R China
[2] Chinese Acad Sci, Inst Biophys, Beijing 100101, Peoples R China
[3] Chinese Acad Sci, Grad Sch, Beijing 100049, Peoples R China
基金
中国国家自然科学基金;
关键词
INTERFERON-GAMMA; LIPID MEDIATORS; LIPOXIN A(4); ANTI-INFLAMMATION; NITRIC-OXIDE; EXPRESSION; CYCLOOXYGENASE-2; CARCINOGENESIS; PHASE;
D O I
10.1155/2013/930124
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Background. Acute inflammation and its timely resolution play important roles in the body's responses to the environmental stimulation. Although IFN-gamma is well known for the induction of inflammation, its role in the inflammation resolution is still poorly understood. Methodology and Principal Findings. In this study, we investigated the function of interferon gamma (IFN-gamma) during the resolution of PMA-induced skin inflammation in vivo. The results revealed that the expression levels of IL-6, TNF-alpha, and monocyte chemoattractant protein 1 (MCP-1) in skin decreased during the resolution stage of PMA-induced inflammation, while IFN-gamma is still maintained at a relatively high level. Neutralization of endogenous IFN-gamma led to accelerated reduction of epidermal thickness and decreased epithelial cell proliferation. Similarly, decreased infiltration of inflammatory cells (Gr1(+) or CD11b(+) cells) and a significant reduction of proinflammatory cytokines were also observed upon the blockade of IFN-gamma. Furthermore, neutralization of IFN-gamma boosted ALOX15 expression of the skin during inflammation resolution. In accordance, application of lipoxin A4 (LXA4, a product of ALOX15) obtained a proresolution effect similar to neutralization of IFN-gamma. These results demonstrated that through upregulating ALOX15-LXA4 pathway, blockage of IFN-gamma can promote the resolution of PMA-induced skin inflammation.
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页数:11
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