{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T20:31:16Z","timestamp":1790973076737,"version":"4.1.0"},"reference-count":29,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2009,1,29]],"date-time":"2009-01-29T00:00:00Z","timestamp":1233187200000},"content-version":"vor","delay-in-days":1399,"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":[[2005,4]]},"abstract":"<jats:p>\n<jats:list list-type=\"explicit-label\">\n<jats:list-item><jats:p>An emerging body of evidence indicates that PGE<jats:sub>2<\/jats:sub> has a privileged anti\u2010inflammatory role within the airways. Stimulants of protease\u2010activated receptor\u20102 (PAR<jats:sub>2<\/jats:sub>) inhibit airway smooth muscle tone <jats:italic>in vitro<\/jats:italic> and <jats:italic>in vivo<\/jats:italic> predominantly <jats:italic>via<\/jats:italic> cyclooxygenase (COX)\u2010dependent generation of prostaglandin E<jats:sub>2<\/jats:sub> (PGE<jats:sub>2<\/jats:sub>). Thus, the current study tested the hypothesis that PAR<jats:sub>2<\/jats:sub>\u2010induced generation of PGE<jats:sub>2<\/jats:sub> inhibits the development of allergic airways inflammation and hyperresponsiveness.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Bronchoalveolar lavage (BAL) fluid recovered from ovalbumin (OVA)\u2010sensitised and \u2010challenged (allergic) mice contained elevated numbers of eosinophils, which peaked at 48\u2003h postchallenge. Intranasal (i.n.) administration of a PAR<jats:sub>2<\/jats:sub>\u2010activating peptide (PAR<jats:sub>2<\/jats:sub>\u2010AP) SLIGRL (25\u2003mg\u2003kg<jats:sup>\u22121<\/jats:sup>, at the time of OVA challenge) caused a 70% reduction in the numbers of BAL eosinophils (compared to the scrambled peptide LSIGRL, 25\u2003mg\u2003kg<jats:sup>\u22121<\/jats:sup>).<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Pretreatment of allergic mice with either indomethacin (1\u2003mg\u2003kg<jats:sup>\u22121<\/jats:sup>, dual COX inhibitor) or nimesulide (3\u2003mg\u2003kg<jats:sup>\u22121<\/jats:sup>, COX\u20102\u2010selective inhibitor) blocked SLIGRL\u2010induced reductions in BAL eosinophils.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>I.n. SLIGRL, but not LSIGRL, inhibited the development of antigen\u2010induced airways hyperresponsiveness. The inhibitory effect of SLIGRL was blocked by indomethacin.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Exposure of isolated tracheal preparations from allergic mice to 100\u2003<jats:italic>\u03bc<\/jats:italic><jats:sc>M<\/jats:sc> SLIGRL was associated with a 5.0\u2010fold increase in PGE<jats:sub>2<\/jats:sub> levels (<jats:italic>P<\/jats:italic>&lt;0.05, compared to 100\u2003<jats:italic>\u03bc<\/jats:italic><jats:sc>M<\/jats:sc> LSIGRL). SLIGRL induced similar increases in PGE<jats:sub>2<\/jats:sub> levels in control mice (OVA\u2010sensitised, saline\u2010challenged).<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>I.n. administration of PGE<jats:sub>2<\/jats:sub> (0.15\u2003mg\u2003kg<jats:sup>\u22121<\/jats:sup>) to allergic mice significantly inhibited eosinophilia and airways hyperresponsiveness to methacholine.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>In anaesthetised, ventilated allergic mice, SLIGRL (5\u2003mg\u2003kg<jats:sup>\u22121<\/jats:sup>, i.v.) inhibited methacholine\u2010induced increases in airways resistance. Consistent with this bronchodilator effect, SLIGRL induced pronounced relaxation responses in isolated tracheal preparations obtained from allergic mice. LSIGRL did not inhibit bronchomotor tone in either of these <jats:italic>in vivo<\/jats:italic> or <jats:italic>in vitro<\/jats:italic> experiments.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>In summary, a PAR<jats:sub>2<\/jats:sub>\u2010AP SLIGRL inhibited the development of airway eosinophilia and hyperresponsiveness in allergic mice through a COX\u2010dependent pathway involving COX\u20102\u2010mediated generation of the anti\u2010inflammatory mediator PGE<jats:sub>2<\/jats:sub>. SLIGRL also displayed bronchodilator activity in allergic mice. These studies support the concept that PAR<jats:sub>2<\/jats:sub> exerts predominantly bronchoprotective actions within allergic murine airways.<\/jats:p><\/jats:list-item>\n<\/jats:list>\n<\/jats:p><jats:p><jats:italic>British Journal of Pharmacology<\/jats:italic> (2005) <jats:bold>144<\/jats:bold>, 1100\u20131108. doi:<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"doi\" xlink:href=\"10.1038\/sj.bjp.0706150\">10.1038\/sj.bjp.0706150<\/jats:ext-link><\/jats:p>","DOI":"10.1038\/sj.bjp.0706150","type":"journal-article","created":{"date-parts":[[2005,2,7]],"date-time":"2005-02-07T15:11:57Z","timestamp":1107789117000},"page":"1100-1108","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":44,"title":["Stimulation of protease\u2010activated receptor\u20102 inhibits airway eosinophilia, hyperresponsiveness and bronchoconstriction in a murine model of allergic inflammation"],"prefix":"10.1111","volume":"144","author":[{"given":"Benjamin A","family":"De Campo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter J","family":"Henry","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2009,1,29]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.97.10.5255"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0952-3278(03)00076-0"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0703738"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/18223"},{"key":"e_1_2_7_6_1","first-page":"671","article-title":"Cardiovascular responses mediated by protease\u2010activated receptor\u20102 (PAR\u20102) and thrombin receptor (PAR\u20101) are distinguished in mice deficient in PAR\u20102 or PAR\u20101","volume":"288","author":"DAMIANO B.P.","year":"1999","journal-title":"J. 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