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

Background. Acute inflammation and its timely resolution play important roles in the body's responses to the environmental stimulation. Although IFN-γ is well known for the induction of inflammation, its role in the inflammation resolution is still poorly understood. Methodology and Principal...

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Main Authors: Zhang, Guojun, Liu, Xiaoman, Wang, Chunhui, Qu, Liwei, Deng, Jingjing, Wang, Hui, Qin, Zhihai
Format: Online
Language:English
Published: Hindawi Publishing Corporation 2013
Online Access:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3683498/
id pubmed-3683498
recordtype oai_dc
spelling pubmed-36834982013-07-01 Resolution of PMA-Induced Skin Inflammation Involves Interaction of IFN-γ and ALOX15 Zhang, Guojun Liu, Xiaoman Wang, Chunhui Qu, Liwei Deng, Jingjing Wang, Hui Qin, Zhihai Research Article Background. Acute inflammation and its timely resolution play important roles in the body's responses to the environmental stimulation. Although IFN-γ 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-γ) during the resolution of PMA-induced skin inflammation in vivo. The results revealed that the expression levels of IL-6, TNF-α, and monocyte chemoattractant protein 1 (MCP-1) in skin decreased during the resolution stage of PMA-induced inflammation, while IFN-γ is still maintained at a relatively high level. Neutralization of endogenous IFN-γ 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-γ. Furthermore, neutralization of IFN-γ 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-γ. These results demonstrated that through upregulating ALOX15-LXA4 pathway, blockage of IFN-γ can promote the resolution of PMA-induced skin inflammation. Hindawi Publishing Corporation 2013 2013-06-02 /pmc/articles/PMC3683498/ /pubmed/23818745 http://dx.doi.org/10.1155/2013/930124 Text en Copyright © 2013 Guojun Zhang et al. https://creativecommons.org/licenses/by/3.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
repository_type Open Access Journal
institution_category Foreign Institution
institution US National Center for Biotechnology Information
building NCBI PubMed
collection Online Access
language English
format Online
author Zhang, Guojun
Liu, Xiaoman
Wang, Chunhui
Qu, Liwei
Deng, Jingjing
Wang, Hui
Qin, Zhihai
spellingShingle Zhang, Guojun
Liu, Xiaoman
Wang, Chunhui
Qu, Liwei
Deng, Jingjing
Wang, Hui
Qin, Zhihai
Resolution of PMA-Induced Skin Inflammation Involves Interaction of IFN-γ and ALOX15
author_facet Zhang, Guojun
Liu, Xiaoman
Wang, Chunhui
Qu, Liwei
Deng, Jingjing
Wang, Hui
Qin, Zhihai
author_sort Zhang, Guojun
title Resolution of PMA-Induced Skin Inflammation Involves Interaction of IFN-γ and ALOX15
title_short Resolution of PMA-Induced Skin Inflammation Involves Interaction of IFN-γ and ALOX15
title_full Resolution of PMA-Induced Skin Inflammation Involves Interaction of IFN-γ and ALOX15
title_fullStr Resolution of PMA-Induced Skin Inflammation Involves Interaction of IFN-γ and ALOX15
title_full_unstemmed Resolution of PMA-Induced Skin Inflammation Involves Interaction of IFN-γ and ALOX15
title_sort resolution of pma-induced skin inflammation involves interaction of ifn-γ and alox15
description Background. Acute inflammation and its timely resolution play important roles in the body's responses to the environmental stimulation. Although IFN-γ 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-γ) during the resolution of PMA-induced skin inflammation in vivo. The results revealed that the expression levels of IL-6, TNF-α, and monocyte chemoattractant protein 1 (MCP-1) in skin decreased during the resolution stage of PMA-induced inflammation, while IFN-γ is still maintained at a relatively high level. Neutralization of endogenous IFN-γ 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-γ. Furthermore, neutralization of IFN-γ 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-γ. These results demonstrated that through upregulating ALOX15-LXA4 pathway, blockage of IFN-γ can promote the resolution of PMA-induced skin inflammation.
publisher Hindawi Publishing Corporation
publishDate 2013
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3683498/
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