Up-Regulation of Annexin-A1 and Lipoxin A.sub.4 in Individuals with Ulcerative Colitis May Promote Mucosal Homeostasis
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.sub.4 (LXA.sub.4) exert counter-regulatory effects on leukocyte recruitment, however to date, the dual/cumulativ...
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| Veröffentlicht in: | PloS one 2012-06, Vol.7 (6), p.e39244 |
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| creator | Vong, Linda Ferraz, Jose G. P Dufton, Neil Panaccione, Remo Beck, Paul L Sherman, Philip M Perretti, Mauro Wallace, John L |
| description | 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.sub.4 (LXA.sub.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. 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.sub.4, AnxA1, and the FPR2/ALX receptor in each patient group using a combination of fluorescence microscopy, biochemical and molecular analyses. Mucosal expression of LXA.sub.4 was elevated exclusively in biopsies from individuals in remission (3-fold, P |
| doi_str_mv | 10.1371/journal.pone.0039244 |
| format | Article |
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P ; Dufton, Neil ; Panaccione, Remo ; Beck, Paul L ; Sherman, Philip M ; Perretti, Mauro ; Wallace, John L</creator><creatorcontrib>Vong, Linda ; Ferraz, Jose G. P ; Dufton, Neil ; Panaccione, Remo ; Beck, Paul L ; Sherman, Philip M ; Perretti, Mauro ; Wallace, John L</creatorcontrib><description>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.sub.4 (LXA.sub.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. 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.sub.4, AnxA1, and the FPR2/ALX receptor in each patient group using a combination of fluorescence microscopy, biochemical and molecular analyses. Mucosal expression of LXA.sub.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. 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.sub.4 and AnxA1 in promoting mucosal homeostasis.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0039244</identifier><language>eng</language><publisher>Public Library of Science</publisher><subject>Analysis ; Annexins ; Fluorescence microscopy ; Homeostasis ; Macrophages ; RNA ; Ulcerative colitis</subject><ispartof>PloS one, 2012-06, Vol.7 (6), p.e39244</ispartof><rights>COPYRIGHT 2012 Public Library of Science</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,860,27901,27902</link.rule.ids></links><search><creatorcontrib>Vong, Linda</creatorcontrib><creatorcontrib>Ferraz, Jose G. 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To define the contribution of these mediators, we measured their expression in biopsies from individuals with UC. 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.sub.4, AnxA1, and the FPR2/ALX receptor in each patient group using a combination of fluorescence microscopy, biochemical and molecular analyses. Mucosal expression of LXA.sub.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. 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.sub.4 and AnxA1 in promoting mucosal homeostasis.</description><subject>Analysis</subject><subject>Annexins</subject><subject>Fluorescence microscopy</subject><subject>Homeostasis</subject><subject>Macrophages</subject><subject>RNA</subject><subject>Ulcerative colitis</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><recordid>eNqNkc9LwzAUx4soOKf_gYeAIHhoTZo23Y5lqBtsKNN5Ha9p0mVkyWjSOf97I3rYwIO8w_vB5_t4P6LomuCE0ILcr23XGtDJ1hqRYEyHaZadRD0ypGnMUkxPD-Lz6MK5NcY5HTDWi3aLbTwXTafBK2uQlag0RuyViUuCwNRoqrY2pKhMXFclGQrhxNRqp-oOtEMfyq_QQnPRhgY7gUZWK68cmsEnemntxnqBZh23DjQa242wzoNT7jI6k0Eurn59P1o8PryNxvH0-WkyKqdxQxhL4xwkZilIRkhRk2JYCcBVGJ0C56JmtBZh_wHQHApSYZENpKyIhLTiMiSFpP3o5qdvA1oslZHWt8A3yvFlmRUFZgXL00Alf1DBarFRPBxVqlA_EtwdCQLjxd430Dm3nLzO_88-vx-ztwfsSoD2K2d19_0bdwh-AUKImcc</recordid><startdate>20120618</startdate><enddate>20120618</enddate><creator>Vong, Linda</creator><creator>Ferraz, Jose G. 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P</creatorcontrib><creatorcontrib>Dufton, Neil</creatorcontrib><creatorcontrib>Panaccione, Remo</creatorcontrib><creatorcontrib>Beck, Paul L</creatorcontrib><creatorcontrib>Sherman, Philip M</creatorcontrib><creatorcontrib>Perretti, Mauro</creatorcontrib><creatorcontrib>Wallace, John L</creatorcontrib><collection>Gale In Context: Opposing Viewpoints</collection><collection>Gale In Context: Science</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Vong, Linda</au><au>Ferraz, Jose G. P</au><au>Dufton, Neil</au><au>Panaccione, Remo</au><au>Beck, Paul L</au><au>Sherman, Philip M</au><au>Perretti, Mauro</au><au>Wallace, John L</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Up-Regulation of Annexin-A1 and Lipoxin A.sub.4 in Individuals with Ulcerative Colitis May Promote Mucosal Homeostasis</atitle><jtitle>PloS one</jtitle><date>2012-06-18</date><risdate>2012</risdate><volume>7</volume><issue>6</issue><spage>e39244</spage><pages>e39244-</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>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.sub.4 (LXA.sub.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. 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.sub.4, AnxA1, and the FPR2/ALX receptor in each patient group using a combination of fluorescence microscopy, biochemical and molecular analyses. Mucosal expression of LXA.sub.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. 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.sub.4 and AnxA1 in promoting mucosal homeostasis.</abstract><pub>Public Library of Science</pub><doi>10.1371/journal.pone.0039244</doi><tpages>e39244</tpages></addata></record> |
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| source | DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; Free Full-Text Journals in Chemistry; Public Library of Science (PLoS) |
| subjects | Analysis Annexins Fluorescence microscopy Homeostasis Macrophages RNA Ulcerative colitis |
| title | Up-Regulation of Annexin-A1 and Lipoxin A.sub.4 in Individuals with Ulcerative Colitis May Promote Mucosal Homeostasis |
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