Up-regulation of Annexin-A1 and lipoxin A(4) in individuals with ulcerative colitis may promote mucosal homeostasis.

<h4>Background</h4>One of the characteristics of an active episode of ulcerative colitis (UC) is the intense mucosal infiltration of leukocytes. The pro-resolution mediators Annexin-A1 (AnxA1) and lipoxin A(4) (LXA(4)) exert counter-regulatory effects on leukocyte recruitment, however to...

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Autores principales:	Linda Vong, Jose G P Ferraz, Neil Dufton, Remo Panaccione, Paul L Beck, Philip M Sherman, Mauro Perretti, John L Wallace
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/af0f69bd424148e9b52e5368f5c370da
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spelling	oai:doaj.org-article:af0f69bd424148e9b52e5368f5c370da2021-11-18T07:15:07ZUp-regulation of Annexin-A1 and lipoxin A(4) in individuals with ulcerative colitis may promote mucosal homeostasis.1932-620310.1371/journal.pone.0039244https://doaj.org/article/af0f69bd424148e9b52e5368f5c370da2012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22723974/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>One of the characteristics of an active episode of ulcerative colitis (UC) is the intense mucosal infiltration of leukocytes. The pro-resolution mediators Annexin-A1 (AnxA1) and lipoxin A(4) (LXA(4)) exert counter-regulatory effects on leukocyte recruitment, however to date, the dual/cumulative effects of these formyl peptide receptor-2 (FPR2/ALX) agonists in the context of human intestinal diseases are unclear. To define the contribution of these mediators, we measured their expression in biopsies from individuals with UC.<h4>Methods</h4>Colonic mucosal biopsies were collected from two broad patient groups: healthy volunteers without ('Ctrl' n = 20) or with a prior history of UC ('hx of UC' n = 5); individuals with UC experiencing active disease ('active' n = 8), or in medically-induced remission ('remission' n = 16). We assessed the mucosal expression of LXA(4), AnxA1, and the FPR2/ALX receptor in each patient group using a combination of fluorescence microscopy, biochemical and molecular analyses.<h4>Results</h4>Mucosal expression of LXA(4) was elevated exclusively in biopsies from individuals in remission (3-fold, P<0.05 vs. Ctrl). Moreover, in this same group we observed an upregulation of AnxA1 protein expression (2.5-fold increase vs. Ctrl, P<.01), concurrent with an increased level of macrophage infiltration, and an elevation in FPR2/ALX mRNA (7-fold increase vs. Ctrl, P<.05). Importantly, AnxA1 expression was not limited to cells infiltrating the lamina propria but was also detected in epithelial cells lining the intestinal crypts.<h4>Conclusions</h4>Our results demonstrate a specific up-regulation of this pro-resolution circuit in individuals in remission from UC, and suggest a significant role for LXA(4) and AnxA1 in promoting mucosal homeostasis.Linda VongJose G P FerrazNeil DuftonRemo PanaccionePaul L BeckPhilip M ShermanMauro PerrettiJohn L WallacePublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 6, p e39244 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Linda Vong Jose G P Ferraz Neil Dufton Remo Panaccione Paul L Beck Philip M Sherman Mauro Perretti John L Wallace Up-regulation of Annexin-A1 and lipoxin A(4) in individuals with ulcerative colitis may promote mucosal homeostasis.
description	<h4>Background</h4>One of the characteristics of an active episode of ulcerative colitis (UC) is the intense mucosal infiltration of leukocytes. The pro-resolution mediators Annexin-A1 (AnxA1) and lipoxin A(4) (LXA(4)) exert counter-regulatory effects on leukocyte recruitment, however to date, the dual/cumulative effects of these formyl peptide receptor-2 (FPR2/ALX) agonists in the context of human intestinal diseases are unclear. To define the contribution of these mediators, we measured their expression in biopsies from individuals with UC.<h4>Methods</h4>Colonic mucosal biopsies were collected from two broad patient groups: healthy volunteers without ('Ctrl' n = 20) or with a prior history of UC ('hx of UC' n = 5); individuals with UC experiencing active disease ('active' n = 8), or in medically-induced remission ('remission' n = 16). We assessed the mucosal expression of LXA(4), AnxA1, and the FPR2/ALX receptor in each patient group using a combination of fluorescence microscopy, biochemical and molecular analyses.<h4>Results</h4>Mucosal expression of LXA(4) was elevated exclusively in biopsies from individuals in remission (3-fold, P<0.05 vs. Ctrl). Moreover, in this same group we observed an upregulation of AnxA1 protein expression (2.5-fold increase vs. Ctrl, P<.01), concurrent with an increased level of macrophage infiltration, and an elevation in FPR2/ALX mRNA (7-fold increase vs. Ctrl, P<.05). Importantly, AnxA1 expression was not limited to cells infiltrating the lamina propria but was also detected in epithelial cells lining the intestinal crypts.<h4>Conclusions</h4>Our results demonstrate a specific up-regulation of this pro-resolution circuit in individuals in remission from UC, and suggest a significant role for LXA(4) and AnxA1 in promoting mucosal homeostasis.
format	article
author	Linda Vong Jose G P Ferraz Neil Dufton Remo Panaccione Paul L Beck Philip M Sherman Mauro Perretti John L Wallace
author_facet	Linda Vong Jose G P Ferraz Neil Dufton Remo Panaccione Paul L Beck Philip M Sherman Mauro Perretti John L Wallace
author_sort	Linda Vong
title	Up-regulation of Annexin-A1 and lipoxin A(4) in individuals with ulcerative colitis may promote mucosal homeostasis.
title_short	Up-regulation of Annexin-A1 and lipoxin A(4) in individuals with ulcerative colitis may promote mucosal homeostasis.
title_full	Up-regulation of Annexin-A1 and lipoxin A(4) in individuals with ulcerative colitis may promote mucosal homeostasis.
title_fullStr	Up-regulation of Annexin-A1 and lipoxin A(4) in individuals with ulcerative colitis may promote mucosal homeostasis.
title_full_unstemmed	Up-regulation of Annexin-A1 and lipoxin A(4) in individuals with ulcerative colitis may promote mucosal homeostasis.
title_sort	up-regulation of annexin-a1 and lipoxin a(4) in individuals with ulcerative colitis may promote mucosal homeostasis.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/af0f69bd424148e9b52e5368f5c370da
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Up-regulation of Annexin-A1 and lipoxin A(4) in individuals with ulcerative colitis may promote mucosal homeostasis.

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