Exendin-4 ameliorates oxidized-LDL-induced inhibition of macrophage migration in vitro via the NF-κB pathway

Aim: To investigate the effects of the glucagon-like peptide-1 (GLP-1) receptor agonist exendin-4 on oxidized low-density lipoprotein (ox-LDL)-induced inhibition of macrophage migration and the mechanisms underlying the effects of exendin-4. Methods: Primary peritoneal macrophages were extracted fro...

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Veröffentlicht in:Acta pharmacologica Sinica 2014-02, Vol.35 (2), p.195-202
Hauptverfasser: Ma, Ge-fei, Chen, Song, Yin, Lei, Gao, Xiang-dong, Yao, Wen-bing
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container_issue 2
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container_title Acta pharmacologica Sinica
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creator Ma, Ge-fei
Chen, Song
Yin, Lei
Gao, Xiang-dong
Yao, Wen-bing
description Aim: To investigate the effects of the glucagon-like peptide-1 (GLP-1) receptor agonist exendin-4 on oxidized low-density lipoprotein (ox-LDL)-induced inhibition of macrophage migration and the mechanisms underlying the effects of exendin-4. Methods: Primary peritoneal macrophages were extracted from the peritoneal cavity of mice treated with 3% thioglycollate (2 mL, ip). Migration of the macrophages was examined using a cell migration assay. Macrophage migration-related factors including leptin-like ox-LDL receptor (LOX-1), cyclooxygenase 2 (COX-2), tumor necrosis factor (TNF)-α, interleukin-1 (IL-1)β, matrix metalloproteinase-2 (MMP-2), intercellular adhesion molecule (ICAM)-1 and macrophage migration inhibitory factor (MIF) were measured using semi-quantitative RT-PCR. Expression of MIF and ICAM-1 proteins was examined with ELISA. Gelatin zymography was used to evaluate the activity of MMP-9. Activation of the NF-κB pathway was determined by confocal laser scanning microscopy. Results: Treatment of the macrophages with ox-LDL (50 μg/mL) markedly suppressed the macrophage migration. Furthermore, ox-LDL treatment substantially increased the expression of the macrophage migration-related factors, the activity of MMP-9 and the translocation of the NF-κB p65 subunit. These effects of ox-LDL were significantly ameliorated by pretreatment with the specific NF-κB inhibitor ammonium pyrrolidine dithiocarbamate (100 μmol/L). These effects of ox-LDL were also significantly ameliorated by pretreatment with exendin-4 (25 and 50 nmol/L). Conclusion: Exendin-4 ameliorates the inhibition of ox-LDL on macrophage migration in vitro , via suppressing ox-LDL-induced expression of ICAM-1 and MIF, which is probably mediated by the NF-κB pathway.
doi_str_mv 10.1038/aps.2013.128
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Methods: Primary peritoneal macrophages were extracted from the peritoneal cavity of mice treated with 3% thioglycollate (2 mL, ip). Migration of the macrophages was examined using a cell migration assay. Macrophage migration-related factors including leptin-like ox-LDL receptor (LOX-1), cyclooxygenase 2 (COX-2), tumor necrosis factor (TNF)-α, interleukin-1 (IL-1)β, matrix metalloproteinase-2 (MMP-2), intercellular adhesion molecule (ICAM)-1 and macrophage migration inhibitory factor (MIF) were measured using semi-quantitative RT-PCR. Expression of MIF and ICAM-1 proteins was examined with ELISA. Gelatin zymography was used to evaluate the activity of MMP-9. Activation of the NF-κB pathway was determined by confocal laser scanning microscopy. Results: Treatment of the macrophages with ox-LDL (50 μg/mL) markedly suppressed the macrophage migration. Furthermore, ox-LDL treatment substantially increased the expression of the macrophage migration-related factors, the activity of MMP-9 and the translocation of the NF-κB p65 subunit. These effects of ox-LDL were significantly ameliorated by pretreatment with the specific NF-κB inhibitor ammonium pyrrolidine dithiocarbamate (100 μmol/L). These effects of ox-LDL were also significantly ameliorated by pretreatment with exendin-4 (25 and 50 nmol/L). Conclusion: Exendin-4 ameliorates the inhibition of ox-LDL on macrophage migration in vitro , via suppressing ox-LDL-induced expression of ICAM-1 and MIF, which is probably mediated by the NF-κB pathway.</description><identifier>ISSN: 1671-4083</identifier><identifier>EISSN: 1745-7254</identifier><identifier>DOI: 10.1038/aps.2013.128</identifier><identifier>PMID: 24335838</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>Animals ; Biomedical and Life Sciences ; Biomedicine ; Cells, Cultured ; Immunology ; Internal Medicine ; Lipoproteins, LDL - metabolism ; Macrophages - drug effects ; Medical Microbiology ; Mice ; Mice, Inbred ICR ; NF-kappa B - metabolism ; Original ; original-article ; Peptides - pharmacology ; Pharmacology/Toxicology ; Signal Transduction - drug effects ; Vaccine ; Venoms - pharmacology</subject><ispartof>Acta pharmacologica Sinica, 2014-02, Vol.35 (2), p.195-202</ispartof><rights>CPS and SIMM 2014</rights><rights>Copyright © 2014 CPS and SIMM 2014 CPS and SIMM</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c422t-fc8e50f91f6316c1418c0761a4b14fae719d05b06c1b30aea3f19b2194b7e6603</citedby><cites>FETCH-LOGICAL-c422t-fc8e50f91f6316c1418c0761a4b14fae719d05b06c1b30aea3f19b2194b7e6603</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4651214/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4651214/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,315,728,781,785,886,27929,27930,53796,53798</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24335838$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Ma, Ge-fei</creatorcontrib><creatorcontrib>Chen, Song</creatorcontrib><creatorcontrib>Yin, Lei</creatorcontrib><creatorcontrib>Gao, Xiang-dong</creatorcontrib><creatorcontrib>Yao, Wen-bing</creatorcontrib><title>Exendin-4 ameliorates oxidized-LDL-induced inhibition of macrophage migration in vitro via the NF-κB pathway</title><title>Acta pharmacologica Sinica</title><addtitle>Acta Pharmacol Sin</addtitle><addtitle>Acta Pharmacol Sin</addtitle><description>Aim: To investigate the effects of the glucagon-like peptide-1 (GLP-1) receptor agonist exendin-4 on oxidized low-density lipoprotein (ox-LDL)-induced inhibition of macrophage migration and the mechanisms underlying the effects of exendin-4. Methods: Primary peritoneal macrophages were extracted from the peritoneal cavity of mice treated with 3% thioglycollate (2 mL, ip). Migration of the macrophages was examined using a cell migration assay. Macrophage migration-related factors including leptin-like ox-LDL receptor (LOX-1), cyclooxygenase 2 (COX-2), tumor necrosis factor (TNF)-α, interleukin-1 (IL-1)β, matrix metalloproteinase-2 (MMP-2), intercellular adhesion molecule (ICAM)-1 and macrophage migration inhibitory factor (MIF) were measured using semi-quantitative RT-PCR. Expression of MIF and ICAM-1 proteins was examined with ELISA. Gelatin zymography was used to evaluate the activity of MMP-9. Activation of the NF-κB pathway was determined by confocal laser scanning microscopy. Results: Treatment of the macrophages with ox-LDL (50 μg/mL) markedly suppressed the macrophage migration. Furthermore, ox-LDL treatment substantially increased the expression of the macrophage migration-related factors, the activity of MMP-9 and the translocation of the NF-κB p65 subunit. These effects of ox-LDL were significantly ameliorated by pretreatment with the specific NF-κB inhibitor ammonium pyrrolidine dithiocarbamate (100 μmol/L). These effects of ox-LDL were also significantly ameliorated by pretreatment with exendin-4 (25 and 50 nmol/L). Conclusion: Exendin-4 ameliorates the inhibition of ox-LDL on macrophage migration in vitro , via suppressing ox-LDL-induced expression of ICAM-1 and MIF, which is probably mediated by the NF-κB pathway.</description><subject>Animals</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Cells, Cultured</subject><subject>Immunology</subject><subject>Internal Medicine</subject><subject>Lipoproteins, LDL - metabolism</subject><subject>Macrophages - drug effects</subject><subject>Medical Microbiology</subject><subject>Mice</subject><subject>Mice, Inbred ICR</subject><subject>NF-kappa B - metabolism</subject><subject>Original</subject><subject>original-article</subject><subject>Peptides - pharmacology</subject><subject>Pharmacology/Toxicology</subject><subject>Signal Transduction - drug effects</subject><subject>Vaccine</subject><subject>Venoms - pharmacology</subject><issn>1671-4083</issn><issn>1745-7254</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNptkMtOAyEUhonR2FrduTY8gFQOMLeNidZr0uhG14SZYTo0HZgw03p5NB_CZ5Km2mjiBsj5Lyd8CB0DHQPl6ZlquzGjwMfA0h00hEREJGGR2A3vOAEiaMoH6KDr5pRyxiHbRwMmOI9Sng5Rc_2qbWksEVg1emGcV73usHs1pXnXJZleTYmx5bLQJTa2NrnpjbPYVbhRhXdtrWYaN2YWYuu5sXhleu_CqXBfa_xwQz4_LnGr-vpFvR2ivUotOn30fY_Q88310-SOTB9v7ycXU1IIxnpSFamOaJVBFXOICxCQFjSJQYkcRKV0AllJo5wGKedUacUryHIGmcgTHceUj9D5prdd5o0uC217rxay9aZR_k06ZeRfxZpaztxKijgCBiIUnG4Kwh-7zutqmwUq19hlwC7X2GXAHuwnv_dtzT-cg4FsDF2Q7Ex7OXdLbwOD_wu_AIx_j8s</recordid><startdate>20140201</startdate><enddate>20140201</enddate><creator>Ma, Ge-fei</creator><creator>Chen, Song</creator><creator>Yin, Lei</creator><creator>Gao, Xiang-dong</creator><creator>Yao, Wen-bing</creator><general>Nature Publishing Group UK</general><general>Nature Publishing Group</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>5PM</scope></search><sort><creationdate>20140201</creationdate><title>Exendin-4 ameliorates oxidized-LDL-induced inhibition of macrophage migration in vitro via the NF-κB pathway</title><author>Ma, Ge-fei ; Chen, Song ; Yin, Lei ; Gao, Xiang-dong ; Yao, Wen-bing</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c422t-fc8e50f91f6316c1418c0761a4b14fae719d05b06c1b30aea3f19b2194b7e6603</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Animals</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>Cells, Cultured</topic><topic>Immunology</topic><topic>Internal Medicine</topic><topic>Lipoproteins, LDL - metabolism</topic><topic>Macrophages - drug effects</topic><topic>Medical Microbiology</topic><topic>Mice</topic><topic>Mice, Inbred ICR</topic><topic>NF-kappa B - metabolism</topic><topic>Original</topic><topic>original-article</topic><topic>Peptides - pharmacology</topic><topic>Pharmacology/Toxicology</topic><topic>Signal Transduction - drug effects</topic><topic>Vaccine</topic><topic>Venoms - pharmacology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ma, Ge-fei</creatorcontrib><creatorcontrib>Chen, Song</creatorcontrib><creatorcontrib>Yin, Lei</creatorcontrib><creatorcontrib>Gao, Xiang-dong</creatorcontrib><creatorcontrib>Yao, Wen-bing</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Acta pharmacologica Sinica</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ma, Ge-fei</au><au>Chen, Song</au><au>Yin, Lei</au><au>Gao, Xiang-dong</au><au>Yao, Wen-bing</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Exendin-4 ameliorates oxidized-LDL-induced inhibition of macrophage migration in vitro via the NF-κB pathway</atitle><jtitle>Acta pharmacologica Sinica</jtitle><stitle>Acta Pharmacol Sin</stitle><addtitle>Acta Pharmacol Sin</addtitle><date>2014-02-01</date><risdate>2014</risdate><volume>35</volume><issue>2</issue><spage>195</spage><epage>202</epage><pages>195-202</pages><issn>1671-4083</issn><eissn>1745-7254</eissn><abstract>Aim: To investigate the effects of the glucagon-like peptide-1 (GLP-1) receptor agonist exendin-4 on oxidized low-density lipoprotein (ox-LDL)-induced inhibition of macrophage migration and the mechanisms underlying the effects of exendin-4. Methods: Primary peritoneal macrophages were extracted from the peritoneal cavity of mice treated with 3% thioglycollate (2 mL, ip). Migration of the macrophages was examined using a cell migration assay. Macrophage migration-related factors including leptin-like ox-LDL receptor (LOX-1), cyclooxygenase 2 (COX-2), tumor necrosis factor (TNF)-α, interleukin-1 (IL-1)β, matrix metalloproteinase-2 (MMP-2), intercellular adhesion molecule (ICAM)-1 and macrophage migration inhibitory factor (MIF) were measured using semi-quantitative RT-PCR. Expression of MIF and ICAM-1 proteins was examined with ELISA. Gelatin zymography was used to evaluate the activity of MMP-9. Activation of the NF-κB pathway was determined by confocal laser scanning microscopy. Results: Treatment of the macrophages with ox-LDL (50 μg/mL) markedly suppressed the macrophage migration. Furthermore, ox-LDL treatment substantially increased the expression of the macrophage migration-related factors, the activity of MMP-9 and the translocation of the NF-κB p65 subunit. These effects of ox-LDL were significantly ameliorated by pretreatment with the specific NF-κB inhibitor ammonium pyrrolidine dithiocarbamate (100 μmol/L). These effects of ox-LDL were also significantly ameliorated by pretreatment with exendin-4 (25 and 50 nmol/L). Conclusion: Exendin-4 ameliorates the inhibition of ox-LDL on macrophage migration in vitro , via suppressing ox-LDL-induced expression of ICAM-1 and MIF, which is probably mediated by the NF-κB pathway.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>24335838</pmid><doi>10.1038/aps.2013.128</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record>
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subjects Animals
Biomedical and Life Sciences
Biomedicine
Cells, Cultured
Immunology
Internal Medicine
Lipoproteins, LDL - metabolism
Macrophages - drug effects
Medical Microbiology
Mice
Mice, Inbred ICR
NF-kappa B - metabolism
Original
original-article
Peptides - pharmacology
Pharmacology/Toxicology
Signal Transduction - drug effects
Vaccine
Venoms - pharmacology
title Exendin-4 ameliorates oxidized-LDL-induced inhibition of macrophage migration in vitro via the NF-κB pathway
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