{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T20:37:12Z","timestamp":1771533432291,"version":"3.50.1"},"reference-count":55,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2009,1,29]],"date-time":"2009-01-29T00:00:00Z","timestamp":1233187200000},"content-version":"vor","delay-in-days":820,"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":[[2006,11]]},"abstract":"<jats:sec><jats:title>Background and purpose:<\/jats:title><jats:p>Glycogen synthase kinase\u20103 (GSK\u20103) is a ubiquitous serine\u2010threonine protein kinase that participates in a multitude of cellular processes and has recently been implicated in the pathophysiology of a number of diseases. The aim of this study was to investigate the effects of GSK\u20103\u03b2 inhibition in a model of acute inflammation. Here, we have investigated the effects of TDZD\u20108, a potent and selective GSK\u20103\u03b2 inhibitor, in a mouse model of carrageenan\u2010induced pleurisy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental approach:<\/jats:title><jats:p>Injection of carrageenan into the pleural cavity of mice elicited an acute inflammatory response characterized by: accumulation of fluid containing a large number of neutrophils (PMNs) in the pleural cavity, infiltration of PMNs in lung tissues and subsequent lipid peroxidation, and increased production of nitrite\/nitrate (NOx), prostaglandin E<jats:sub>2<\/jats:sub>(PGE<jats:sub>2<\/jats:sub>), tumour necrosis factor\u2010\u03b1, (TNF\u2010\u03b1) and interleukin\u20101\u03b2 (IL\u20101\u03b2). Furthermore, carrageenan induced an upregulation of the adhesion molecules ICAM\u20101 and P\u2010selectin, iNOS, COX\u20102 as well as nitrotyrosine as determined by immunohistochemical analysis of lung tissues.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key results:<\/jats:title><jats:p>Administration of TDZD\u20108 (1, 3 or 10\u2003mg\u2003kg<jats:sup>\u22121<\/jats:sup>, i.p.), 30\u2003min prior to injection of carrageenan, caused a dose\u2010dependent reduction in all the parameters of inflammation measured.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions and Implications:<\/jats:title><jats:p>Thus, based on these findings we propose that inhibitors of the activity of GSK\u20103\u03b2, such as TDZD\u20108, may be useful in the treatment of various inflammatory diseases.<\/jats:p><jats:p><jats:italic>British Journal of Pharmacology<\/jats:italic>(2006)<jats:bold>149<\/jats:bold>, 687\u2013702. doi:<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"doi\" xlink:href=\"10.1038\/sj.bjp.0706902\">10.1038\/sj.bjp.0706902<\/jats:ext-link><\/jats:p><\/jats:sec>","DOI":"10.1038\/sj.bjp.0706902","type":"journal-article","created":{"date-parts":[[2006,10,3]],"date-time":"2006-10-03T11:10:04Z","timestamp":1159873804000},"page":"687-702","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":48,"title":["Inhibition of glycogen synthase kinase\u20103\u03b2 attenuates the development of carrageenan\u2010induced lung injury in mice"],"prefix":"10.1111","volume":"149","author":[{"given":"S","family":"Cuzzocrea","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C","family":"Crisafulli","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"E","family":"Mazzon","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"E","family":"Esposito","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C","family":"Mui\u00e0","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M","family":"Abdelrahman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R","family":"Di Paola","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C","family":"Thiemermann","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2009,1,29]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1021\/cr000110o"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1042\/bj3020723"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1021\/tx9501445"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/376167a0"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/1097-4547(20000701)61:1<21::AID-JNR3>3.0.CO;2-7"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.C400442200"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1023\/A:1013517013069"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1086\/314839"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/378785a0"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0702275"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.106.102863"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1164\/ajrccm.162.5.9912125"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clim.2006.03.005"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-2952(01)00908-X"},{"key":"e_1_2_8_16_1","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1016\/S0031-6997(24)01484-4","article-title":"Antioxidant therapy: a new pharmacological approach in shock, inflammation, and ischemia\/reperfusion injury","volume":"53","author":"Cuzzocrea S","year":"2001","journal-title":"Pharmacol Rev"},{"key":"e_1_2_8_17_1","doi-asserted-by":"crossref","first-page":"5094","DOI":"10.4049\/jimmunol.163.9.5094","article-title":"Role of IL\u20106 in the pleurisy and lung injury caused by carrageenan","volume":"163","author":"Cuzzocrea S","year":"1999","journal-title":"J Immunol"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M305676200"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.CCM.0000178350.21839.44"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/34923"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1432-1033.1980.tb06059.x"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI117842"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1042\/bj3590001"},{"key":"e_1_2_8_24_1","first-page":"306","article-title":"Arthritogenic actions of recombinant IL\u20101 and tumour necrosis factor a in the rabbit: evidence for synergistic interactions between cytokines in vivo","volume":"75","author":"Henderson B","year":"1989","journal-title":"Clin Exp Immunol"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.2002.01269.x"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-2952(01)00541-X"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.284.5412.321"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.gt.3300785"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni1221"},{"key":"e_1_2_8_30_1","doi-asserted-by":"crossref","first-page":"2132","DOI":"10.4049\/jimmunol.151.4.2132","article-title":"Microglial cell cytotoxicity of oligodendrocytes is mediated through nitric oxide","volume":"151","author":"Merrill JE","year":"1993","journal-title":"J Immunol"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1136\/ard.2004.025619"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/0160-5402(85)90029-4"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/0003-2697(79)90738-3"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/43466"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.32.19929"},{"key":"e_1_2_8_36_1","first-page":"510","article-title":"Evolution of collagen arthritis is arrested by treatment with anti\u2010tumour necrosis factor (TNF) antibody or a recombinant soluble TNF receptor","volume":"77","author":"Piguet PF","year":"1992","journal-title":"J Immunol"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0701180"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1038\/322547a0"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI118035"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1006\/pupt.2002.0374"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.1996.tb15475.x"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-2952(97)00530-3"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1002\/j.1460-2075.1991.tb07761.x"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00016.2002"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(19)50326-X"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.25.19.8444-8455.2005"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M403449200"},{"key":"e_1_2_8_48_1","first-page":"1295","article-title":"The nitric oxide synthase inhibitor, L\u2010N G \u2010monomethylarginine, reduces carrageenan\u2010induced pleurisy in the rat","volume":"273","author":"Tracey WR","year":"1995","journal-title":"J Pharmacol Exp Ther"},{"key":"e_1_2_8_49_1","doi-asserted-by":"publisher","DOI":"10.1358\/dnp.2003.16.9.829337"},{"key":"e_1_2_8_50_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.21.13150"},{"key":"e_1_2_8_51_1","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1136\/ard.2004.028266","article-title":"Nuclear factor (NF)\u2010kappaB proteins: therapeutic targets","volume":"2","author":"Verma IM","year":"2004","journal-title":"Ann Rheum Dis"},{"key":"e_1_2_8_52_1","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.1999.1606"},{"key":"e_1_2_8_53_1","doi-asserted-by":"publisher","DOI":"10.1038\/375408a0"},{"key":"e_1_2_8_54_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0706509"},{"key":"e_1_2_8_55_1","first-page":"RE12","article-title":"Judging a protein by more than its name: GSK\u20103","volume":"100","author":"Woodgett JR","year":"2001","journal-title":"Sci STKE"},{"key":"e_1_2_8_56_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780360915"}],"container-title":["British Journal of Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1038%2Fsj.bjp.0706902","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1038%2Fsj.bjp.0706902","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1038\/sj.bjp.0706902","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,1,11]],"date-time":"2025-01-11T02:59:27Z","timestamp":1736564367000},"score":1,"resource":{"primary":{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/10.1038\/sj.bjp.0706902"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2006,11]]},"references-count":55,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2006,11]]}},"alternative-id":["10.1038\/sj.bjp.0706902"],"URL":"https:\/\/doi.org\/10.1038\/sj.bjp.0706902","archive":["Portico"],"relation":{},"ISSN":["0007-1188","1476-5381"],"issn-type":[{"value":"0007-1188","type":"print"},{"value":"1476-5381","type":"electronic"}],"subject":[],"published":{"date-parts":[[2006,11]]},"assertion":[{"value":"2009-01-29","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}