{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,20]],"date-time":"2026-02-20T00:17:27Z","timestamp":1771546647861,"version":"3.50.1"},"reference-count":39,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2009,2,3]],"date-time":"2009-02-03T00:00:00Z","timestamp":1233619200000},"content-version":"vor","delay-in-days":3808,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[1998,9]]},"abstract":"<jats:p>\n<jats:list list-type=\"explicit-label\">\n<jats:list-item><jats:p>Ligands of the various adenosine receptor subtypes modulate the production of pro\u2010and anti\u2010inflammatory cytokines. Here we evaluated the effect of adenosine and various ligands of the adenosine receptor subtypes (A<jats:sub>1<\/jats:sub>, A<jats:sub>2<\/jats:sub>, A<jats:sub>3<\/jats:sub>) on the chemokine macrophage inflammatory protein (MIP) 1\u03b1 production in immunostimulated RAW macrophages <jats:italic>in vitro<\/jats:italic>. Furthermore, we studied whether a selected A<jats:sub>3<\/jats:sub> adenosine receptor agonist inhibits MIP\u20101\u03b1 production and affects the course of inflammation in collagen\u2010induced arthritis.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>In the cultured macrophages, the A<jats:sub>3<\/jats:sub> receptor agonist <jats:italic>N<\/jats:italic><jats:sup><jats:italic>6<\/jats:italic><\/jats:sup>\u2010(3\u2010iodobenzyl)\u2010adenosine\u20105\u2032\u2010<jats:italic>N<\/jats:italic>\u2010methyluronamide (IB\u2010MECA), and, less potently, the A<jats:sub>2<\/jats:sub> receptor agonist 2\u2010p\u2010(2\u2010carboxyethyl) phenethylamino\u20105\u2032\u2010N\u2010ethyl\u2010carboxamidoadenosine (CGS; 1\u2013200\u2003\u03bc<jats:sc>M<\/jats:sc>) dose\u2010dependently suppressed the production of MIP\u20101\u03b1. The selective A<jats:sub>1<\/jats:sub> receptor agonist 2\u2010chloro\u2010N6\u2010cyclopentyladenosine (CCPA, 1\u2013200\u2003\u03bc<jats:sc>M<\/jats:sc>) was ineffective, and adenosine was a weak inhibitor. The inhibition of MIP\u20101\u03b1 production by the A<jats:sub>3<\/jats:sub> and A<jats:sub>2<\/jats:sub> agonist was associated with suppression of its steady\u2010state mRNA levels.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Based on the <jats:italic>in vitro<\/jats:italic> data, we concluded that activation of A<jats:sub>3<\/jats:sub>, and to a lesser extent A<jats:sub>2<\/jats:sub> adenosine receptors suppresses MIP\u20101\u03b1 expression. Since IB\u2010MECA was the most potent inhibitor of MIP\u20101\u03b1 expression, we next investigated whether it affects the production of other pro\u2010inflammatory mediators. We observed that IB\u2010MECA (1\u2013300\u2003\u03bc<jats:sc>M<\/jats:sc>) inhibited, in a dose\u2010dependent manner, the production of IL\u201012, IL\u20106, and, to a lesser extent, nitric oxide in the immunostimulated cultured macrophages.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Since MIP\u2010\u03b1 is a chemokine which enhances neutrophil recruitment into inflammatory sites, we investigated whether the A<jats:sub>3<\/jats:sub> agonist IB\u2010MECA affects the course of inflammation, MIP\u2010\u03b1 production and the degree of neutrophil recruitment in arthritis. In a model of collagen\u2010induced arthritis in mice, IB\u2010MECA (0.5\u2003mg\/kg\/day) reduced the severity of joint inflammation. IB\u2010MECA inhibited the formation of MIP\u20101\u03b1, IL\u201012 and nitrotyrosine (an indicator of reactive nitrogen species) in the paws, and suppressed neutrophil infiltration.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>We conclude that adenosine receptor agonists, most notably the A<jats:sub>3<\/jats:sub> agonist IB\u2010MECA suppress the production of MIP\u2010\u03b1, and exert anti\u2010inflammatory effects. Therefore, stimulation of adenosine receptor subtypes A<jats:sub>3<\/jats:sub> and A<jats:sub>2<\/jats:sub> may be a strategy worthy of further evaluation for the abrogation of acute or chronic inflammatory disorders.<\/jats:p><\/jats:list-item>\n<\/jats:list>\n<\/jats:p><jats:p><jats:italic>British Journal of Pharmacology<\/jats:italic> (1998) <jats:bold>125<\/jats:bold>, 379\u2013387; doi:<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"doi\" xlink:href=\"10.1038\/sj.bjp.0702040\">10.1038\/sj.bjp.0702040<\/jats:ext-link><\/jats:p>","DOI":"10.1038\/sj.bjp.0702040","type":"journal-article","created":{"date-parts":[[2005,1,28]],"date-time":"2005-01-28T19:49:05Z","timestamp":1106941745000},"page":"379-387","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":152,"title":["Suppression of macrophage inflammatory protein (MIP)\u20101<i>\u03b1<\/i> production and collagen\u2010induced arthritis by adenosine receptor agonists"],"prefix":"10.1111","volume":"125","author":[{"given":"Csaba","family":"Szab\u00f3","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gwen S","family":"Scott","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"L\u00e1szl\u00f3","family":"Vir\u00e1g","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Greg","family":"Egnaczyk","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew L","family":"Salzman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas P","family":"Shanley","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gy\u00f6rgy","family":"Hask\u00f3","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2009,2,3]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2249.1996.d01-836.x"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.80.6.800"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.1996.271.5.C1424"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/0165-6147(93)90094-Z"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/0014-2999(94)00672-T"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1152\/jappl.1994.76.1.5"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.88.6.2441"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI116884"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780380804"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.1993.265.3.C577"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/34923"},{"key":"e_1_2_6_13_1","doi-asserted-by":"crossref","first-page":"5853","DOI":"10.4049\/jimmunol.152.12.5853","article-title":"Protective effect of an adenosine kinase inhibitor in septic shock","volume":"152","author":"Firestein G.S.","year":"1994","journal-title":"J. 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