The PSMP-CCR2 interactions trigger monocyte/macrophage-dependent colitis
Abstract Monocytes/macrophages have been found to be an important component of colitis. However, the key chemokine that initiates the CCR2+ monocytes migration from circulation to colitis tissue remains to be undiscovered. PC3-secreted microprotein (PSMP) is a novel chemokine whose receptor is CCR2....
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Nature Portfolio
2017
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oai:doaj.org-article:3cbfbbfc63c74b4a87367152c720eb022021-12-02T11:52:39ZThe PSMP-CCR2 interactions trigger monocyte/macrophage-dependent colitis10.1038/s41598-017-05255-72045-2322https://doaj.org/article/3cbfbbfc63c74b4a87367152c720eb022017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-05255-7https://doaj.org/toc/2045-2322Abstract Monocytes/macrophages have been found to be an important component of colitis. However, the key chemokine that initiates the CCR2+ monocytes migration from circulation to colitis tissue remains to be undiscovered. PC3-secreted microprotein (PSMP) is a novel chemokine whose receptor is CCR2. The physiological and pathological functions of PSMP have not yet been reported. In this study, PSMP was found to be expressed in colitis and colonic tumor tissues from patients and significantly up-regulated in mouse DSS-induced colitis tissues. PSMP overexpression in the colon aggravated the DSS-induced colitis and the anti-PSMP neutralizing antibody mollified the colitis by reducing macrophage infiltration and inhibiting the expression of IL-6, TNF-α and CCL2. Furthermore, we demonstrated that lipopolysaccharide and muramyl dipeptide induced PSMP expression in the colonic epithelial cells. PSMP was up-regulated in the initial stage prior to IL-6, TNF-α and CCL2 up-regulated expression in DSS colitis and promoted the M1 macrophages to produce CCL2. PSMP chemo-attracted Ly6Chi monocytes in a CCR2 dependent manner via in situ chemotaxis and adoptive transfer assays. Our data identify PSMP as a key molecule in ulcerative colitis, which provides a novel mechanism of monocyte/macrophage migration that affects gut innate immunity and makes PSMP a potential target for controlling colitis.Xiaolei PeiDanfeng ZhengShaoping SheJing MaChangyuan GuoXiaoning MoYingmei ZhangQuansheng SongYu ZhangDalong MaYing WangNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-14 (2017) |
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Medicine R Science Q Xiaolei Pei Danfeng Zheng Shaoping She Jing Ma Changyuan Guo Xiaoning Mo Yingmei Zhang Quansheng Song Yu Zhang Dalong Ma Ying Wang The PSMP-CCR2 interactions trigger monocyte/macrophage-dependent colitis |
description |
Abstract Monocytes/macrophages have been found to be an important component of colitis. However, the key chemokine that initiates the CCR2+ monocytes migration from circulation to colitis tissue remains to be undiscovered. PC3-secreted microprotein (PSMP) is a novel chemokine whose receptor is CCR2. The physiological and pathological functions of PSMP have not yet been reported. In this study, PSMP was found to be expressed in colitis and colonic tumor tissues from patients and significantly up-regulated in mouse DSS-induced colitis tissues. PSMP overexpression in the colon aggravated the DSS-induced colitis and the anti-PSMP neutralizing antibody mollified the colitis by reducing macrophage infiltration and inhibiting the expression of IL-6, TNF-α and CCL2. Furthermore, we demonstrated that lipopolysaccharide and muramyl dipeptide induced PSMP expression in the colonic epithelial cells. PSMP was up-regulated in the initial stage prior to IL-6, TNF-α and CCL2 up-regulated expression in DSS colitis and promoted the M1 macrophages to produce CCL2. PSMP chemo-attracted Ly6Chi monocytes in a CCR2 dependent manner via in situ chemotaxis and adoptive transfer assays. Our data identify PSMP as a key molecule in ulcerative colitis, which provides a novel mechanism of monocyte/macrophage migration that affects gut innate immunity and makes PSMP a potential target for controlling colitis. |
format |
article |
author |
Xiaolei Pei Danfeng Zheng Shaoping She Jing Ma Changyuan Guo Xiaoning Mo Yingmei Zhang Quansheng Song Yu Zhang Dalong Ma Ying Wang |
author_facet |
Xiaolei Pei Danfeng Zheng Shaoping She Jing Ma Changyuan Guo Xiaoning Mo Yingmei Zhang Quansheng Song Yu Zhang Dalong Ma Ying Wang |
author_sort |
Xiaolei Pei |
title |
The PSMP-CCR2 interactions trigger monocyte/macrophage-dependent colitis |
title_short |
The PSMP-CCR2 interactions trigger monocyte/macrophage-dependent colitis |
title_full |
The PSMP-CCR2 interactions trigger monocyte/macrophage-dependent colitis |
title_fullStr |
The PSMP-CCR2 interactions trigger monocyte/macrophage-dependent colitis |
title_full_unstemmed |
The PSMP-CCR2 interactions trigger monocyte/macrophage-dependent colitis |
title_sort |
psmp-ccr2 interactions trigger monocyte/macrophage-dependent colitis |
publisher |
Nature Portfolio |
publishDate |
2017 |
url |
https://doaj.org/article/3cbfbbfc63c74b4a87367152c720eb02 |
work_keys_str_mv |
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