{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T20:10:40Z","timestamp":1790799040844,"version":"4.1.0"},"reference-count":78,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2014,3,4]],"date-time":"2014-03-04T00:00:00Z","timestamp":1393891200000},"content-version":"vor","delay-in-days":3,"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":[[2014,3]]},"abstract":"Background and Purpose<\/jats:title>Cannabinoid CB2<\/jats:sub><\/jats:styled-content> receptors mediate immunomodulation. Here, we investigated the effects of CB2<\/jats:sub> receptor ligands on leukocyte\u2010endothelial adhesion and inflammatory mediator release in experimental endotoxin\u2010induced uveitis (EIU<\/jats:styled-content>).<\/jats:p><\/jats:sec>Experimental Approach<\/jats:title>EIU<\/jats:styled-content> was induced by intraocular injection of lipopolysaccharide (LPS<\/jats:styled-content>, 20\u2009ng\u00b7\u03bcL\u22121<\/jats:sup>). Effects of the CB2<\/jats:sub> receptor agonist, HU308<\/jats:styled-content> (1.5% topical), the CB2<\/jats:sub> receptor antagonist, AM630<\/jats:styled-content> (2.5\u2009mg\u00b7kg\u22121<\/jats:sup> i.v.), or a combination of both compounds on leukocyte\u2010endothelial interactions were measured hourly for 6\u2009h in rat iridial vasculature using intravital microscopy. Anti\u2010inflammatory actions of HU308<\/jats:styled-content> were compared with those of clinical treatments for uveitis \u2010 dexamethasone, prednisolone and nepafenac. Transcription factors (NF<\/jats:styled-content>\u2010\u03baB, AP<\/jats:styled-content>\u20101) and inflammatory mediators (cytokines, chemokines and adhesion molecules) were measured in iris and ciliary body tissue.<\/jats:p><\/jats:sec>Key Results<\/jats:title>Leukocyte\u2010endothelium adherence was increased in iridial microvasculature between 4\u20136\u2009h after LPS<\/jats:styled-content>. HU308<\/jats:styled-content> reduced this effect after LPS<\/jats:styled-content> injection and decreased pro\u2010inflammatory mediators: TNF<\/jats:styled-content>\u2010\u03b1, IL<\/jats:styled-content>\u20101\u03b2, IL<\/jats:styled-content>\u20106, CCL5<\/jats:styled-content> and CXCL2<\/jats:styled-content>. AM630<\/jats:styled-content> blocked the actions of HU<\/jats:styled-content>\u2010308, and increased leukocyte\u2010endothelium adhesion. HU<\/jats:styled-content>\u2010308 decreased levels of the transcription factors NF<\/jats:styled-content>\u2010\u03baB and AP<\/jats:styled-content>\u20101, while AM630 increased levels of NF<\/jats:styled-content>\u2010\u03baB. Topical treatments with dexamethasone, prednisolone or nepafenac, failed to alter leukocyte adhesion or mitigate LPS<\/jats:styled-content>\u2010induced increases in inflammatory mediators during the 6\u2009h of EIU<\/jats:styled-content>.<\/jats:p><\/jats:sec>Conclusion and Implications<\/jats:title>Activation of CB2<\/jats:sub> receptors was anti\u2010inflammatory in a model of acute EIU<\/jats:styled-content> and involved a reduction in NF<\/jats:styled-content>\u2010\u03baB, AP<\/jats:styled-content>\u20101 and inflammatory mediators. CB2<\/jats:sub> receptors may be promising drug targets for the development of novel ocular anti\u2010inflammatory agents.<\/jats:p><\/jats:sec>Linked Articles<\/jats:title>This article is part of a themed section on Cannabinoids 2013. To view the other articles in this section visit http:\/\/dx.doi.org\/10.1111\/bph.2014.171.issue\u20106<\/jats:ext-link><\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.12545","type":"journal-article","created":{"date-parts":[[2013,12,6]],"date-time":"2013-12-06T11:46:44Z","timestamp":1386330404000},"page":"1448-1461","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":87,"title":["Anti\u2010inflammatory effects of cannabinoid CB2<\/sub> receptor activation in endotoxin\u2010induced uveitis"],"prefix":"10.1111","volume":"171","author":[{"given":"J T","family":"Toguri","sequence":"first","affiliation":[{"name":"Department of Pharmacology Dalhousie University Halifax NS Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C","family":"Lehmann","sequence":"additional","affiliation":[{"name":"Department of Pharmacology Dalhousie University Halifax NS Canada"},{"name":"Department of Microbiology and Immunology Dalhousie 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