{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,12]],"date-time":"2025-11-12T13:45:19Z","timestamp":1762955119455},"reference-count":82,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2013,5,16]],"date-time":"2013-05-16T00:00:00Z","timestamp":1368662400000},"content-version":"vor","delay-in-days":0,"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":[[2013,6]]},"abstract":"<jats:sec><jats:title>Background and Purpose<\/jats:title><jats:p>Gender differences in inflammation are well described, with females often showing more robust, oestrogen\u2010associated responses. Here, we investigated the influence of gender, oestrogen and the anti\u2010inflammatory protein annexin <jats:styled-content style=\"fixed-case\">A<\/jats:styled-content>1 (<jats:styled-content style=\"fixed-case\">AnxA1<\/jats:styled-content>) on lipopolysaccharide (<jats:styled-content style=\"fixed-case\">LPS<\/jats:styled-content>)\u2010induced leukocyte\u2013endothelial cell interactions in murine cerebral and mesenteric microvascular beds.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental Approach<\/jats:title><jats:p>Intravital microscopy was used to visualize and quantify the effects of <jats:styled-content style=\"fixed-case\">LPS<\/jats:styled-content> (10\u2009\u03bcg\u00b7per mouse i.p.) on leukocyte\u2013endothelial interactions in male and female wild\u2010type (<jats:styled-content style=\"fixed-case\">WT<\/jats:styled-content>) mice. The effects of ovariectomy \u00b1 oestrogen replacement were examined in <jats:styled-content style=\"fixed-case\">WT<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">AnxA1<\/jats:styled-content>\u2010null (<jats:styled-content style=\"fixed-case\">AnxA1<\/jats:styled-content><jats:sup>\u2212\/\u2212<\/jats:sup>) female mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p><jats:styled-content style=\"fixed-case\">LPS<\/jats:styled-content> increased leukocyte adherence in the cerebral and mesenteric beds of both male and female <jats:styled-content style=\"fixed-case\">WT<\/jats:styled-content> mice; females showed exacerbated responses in the brain versus males, but not the mesentery. Ovariectomy further enhanced <jats:styled-content style=\"fixed-case\">LPS<\/jats:styled-content>\u2010induced adhesion in the brain but not the mesentery; its effects were reversed by oestrogen treatment. <jats:styled-content style=\"fixed-case\">OVX AnxA1<\/jats:styled-content><jats:sup>\u2212\/\u2212<\/jats:sup> mice also showed exaggerated adhesive responses to <jats:styled-content style=\"fixed-case\">LPS<\/jats:styled-content> in the brain. However, these were unresponsive to ovariectomy and, paradoxically, responded to oestrogen with a pronounced increase in basal and <jats:styled-content style=\"fixed-case\">LPS<\/jats:styled-content>\u2010induced leukocyte adhesion in the cerebrovasculature.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions and Implications<\/jats:title><jats:p>Our data confirm the fundamental role of <jats:styled-content style=\"fixed-case\">AnxA1<\/jats:styled-content> in limiting the inflammatory response in the central and peripheral microvasculature. They also (i) show that oestrogen acts via an <jats:styled-content style=\"fixed-case\">AnxA1<\/jats:styled-content>\u2010dependent mechanism to protect the cerebral, but not the mesenteric, vasculature from the damaging effects of <jats:styled-content style=\"fixed-case\">LPS<\/jats:styled-content> and (ii) reveal a paradoxical and potentially toxic effect of the steroid in potentiating the central response to <jats:styled-content style=\"fixed-case\">LPS<\/jats:styled-content> in the absence of <jats:styled-content style=\"fixed-case\">AnxA1<\/jats:styled-content>.<\/jats:p><\/jats:sec>","DOI":"10.1111\/j.1476-5381.2012.02146.x","type":"journal-article","created":{"date-parts":[[2012,8,17]],"date-time":"2012-08-17T10:28:28Z","timestamp":1345199308000},"page":"539-553","update-policy":"http:\/\/dx.doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Role and interactions of annexin <scp>A<\/scp>1 and oestrogens in the manifestation of sexual dimorphisms in cerebral and systemic inflammation"],"prefix":"10.1111","volume":"169","author":[{"given":"Ellen L","family":"Hughes","sequence":"first","affiliation":[{"name":"Wolfson Neuroscience Laboratories Imperial College London  London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patricia O","family":"Cover","sequence":"additional","affiliation":[{"name":"Wolfson Neuroscience Laboratories Imperial College London  London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julia C","family":"Buckingham","sequence":"additional","affiliation":[{"name":"Division of Diabetes, Endocrinology and Metabolism, Department of Medicine Imperial College London  London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Felicity NE","family":"Gavins","sequence":"additional","affiliation":[{"name":"Wolfson Neuroscience Laboratories Imperial College London  London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2013,5,16]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2249.2001.01370.x"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.2174\/092986708784872393"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.1998.tb09617.x"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF01487743"},{"key":"e_1_2_8_6_1","first-page":"99","article-title":"Prolactin triggers pro\u2010inflammatory immune responses in peripheral immune cells","volume":"15","author":"Brand JM","year":"2004","journal-title":"Eur Cytokine Netw"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.regpep.2010.09.001"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd1854"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.180.12.7980"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI118774"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.0405206"},{"key":"e_1_2_8_12_1","unstructured":"CoverP McCulleyC JohnC MorrisJ ChristianH BuckinghamJ(2009).Annexin 1 gene deletion induces gender\u2010specific changes in brain dopaminergic systems and prolactin secretion and their sensitivity to modulation by sex\u2010steroids. BPS Winter Meeting 2009. Available at:http:\/\/www.pa2online.org\/abstract\/abstract.jsp?abid=29507."},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.shk.0000232589.39001.4d"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0889-857X(05)70171-X"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF03401853"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.2174\/1381612053381693"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1385\/ENDO:29:2:243"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.imbio.2004.06.001"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)62471-6"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M704096200"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1080\/10739680490266207"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0897.1997.tb00275.x"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1196\/annals.1365.015"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/laban0411-119"},{"key":"e_1_2_8_25_1","first-page":"640","article-title":"Alterations of annexin expression in pathological neuronal and glial reactions. Immunohistochemical localization of annexins I, II (p36 and p11 subunits), IV, and VI in the human hippocampus","volume":"145","author":"Eberhard DA","year":"1994","journal-title":"Am J Pathol"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1097\/00024382-199902000-00004"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.79.3.560"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00595-004-2958-3"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi00051a016"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1056-8719(03)00057-1"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2002-11-3411"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.06-7842com"},{"key":"e_1_2_8_33_1","first-page":"464","article-title":"Neurosteroid levels are increased in vivo after LPS treatment and negatively regulate LPS\u2010induced TNF production","volume":"11","author":"Ghezzi P","year":"2000","journal-title":"Eur Cytokine Netw"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.02-0239fje"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.158.4.1825"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M701541200"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1515\/bchm3.1992.373.1.213"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1186\/1742-2094-8-42"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.vascn.2010.01.004"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2008.12.048"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1095\/biolreprod61.1.171"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneuroim.2006.01.019"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mce.2004.07.010"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0378-5122(03)00279-2"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-291X(02)00807-0"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.2174\/1568016052773333"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.2010.00872.x"},{"key":"e_1_2_8_48_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.103.15.1961"},{"key":"e_1_2_8_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsycho.2004.11.009"},{"key":"e_1_2_8_50_1","doi-asserted-by":"publisher","DOI":"10.1097\/TA.0b013e3181bb9878"},{"key":"e_1_2_8_51_1","doi-asserted-by":"publisher","DOI":"10.1677\/jme.0.0320689"},{"key":"e_1_2_8_52_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri2156"},{"key":"e_1_2_8_53_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1002248"},{"key":"e_1_2_8_54_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.2010.00873.x"},{"key":"e_1_2_8_55_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.2003-0833"},{"key":"e_1_2_8_56_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1112062"},{"key":"e_1_2_8_57_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.1993.tb13563.x"},{"key":"e_1_2_8_58_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2826.2006.01481.x"},{"key":"e_1_2_8_59_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2004-1230"},{"key":"e_1_2_8_60_1","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.111.235176"},{"key":"e_1_2_8_61_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.85.4.377"},{"key":"e_1_2_8_62_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.2514"},{"key":"e_1_2_8_63_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000043631.25915.E6"},{"key":"e_1_2_8_64_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.174.2.305"},{"key":"e_1_2_8_65_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cjca.2010.12.040"},{"key":"e_1_2_8_66_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2011-03-340281"},{"key":"e_1_2_8_67_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.87.1.19"},{"key":"e_1_2_8_68_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.165.3.1573"},{"key":"e_1_2_8_69_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tips.2007.12.003"},{"key":"e_1_2_8_70_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.174.10.6391"},{"key":"e_1_2_8_71_1","doi-asserted-by":"publisher","DOI":"10.1210\/mend-3-3-481"},{"key":"e_1_2_8_72_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.179.12.8533"},{"key":"e_1_2_8_73_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-2999(97)01201-6"},{"key":"e_1_2_8_74_1","doi-asserted-by":"publisher","DOI":"10.1210\/er.2007-0001"},{"key":"e_1_2_8_75_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.1992.263.4.E632"},{"key":"e_1_2_8_76_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0169-328X(02)00383-2"},{"key":"e_1_2_8_77_1","doi-asserted-by":"publisher","DOI":"10.1080\/10739680590904982"},{"key":"e_1_2_8_78_1","doi-asserted-by":"publisher","DOI":"10.1080\/10739680600777599"},{"key":"e_1_2_8_79_1","doi-asserted-by":"publisher","DOI":"10.1677\/JOE-08-0070"},{"key":"e_1_2_8_80_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1000119"},{"key":"e_1_2_8_81_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1098-1136(199906)26:4<333::AID-GLIA7>3.0.CO;2-S"},{"key":"e_1_2_8_82_1","doi-asserted-by":"crossref","first-page":"1890","DOI":"10.4049\/jimmunol.148.6.1890","article-title":"Cytokine production after intravenous or peritoneal gram\u2010negative bacterial challenge in mice. Comparative protective efficacy of antibodies to tumor necrosis factor\u2010alpha and to lipopolysaccharide","volume":"148","author":"Zanetti G","year":"1992","journal-title":"J Immunol"},{"key":"e_1_2_8_83_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0901309"}],"container-title":["British Journal of Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fj.1476-5381.2012.02146.x","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/j.1476-5381.2012.02146.x","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,30]],"date-time":"2023-10-30T14:52:19Z","timestamp":1698677539000},"score":1,"resource":{"primary":{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/10.1111\/j.1476-5381.2012.02146.x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,5,16]]},"references-count":82,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2013,6]]}},"alternative-id":["10.1111\/j.1476-5381.2012.02146.x"],"URL":"https:\/\/doi.org\/10.1111\/j.1476-5381.2012.02146.x","archive":["Portico"],"relation":{},"ISSN":["0007-1188","1476-5381"],"issn-type":[{"value":"0007-1188","type":"print"},{"value":"1476-5381","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,5,16]]},"assertion":[{"value":"2012-03-18","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2012-06-22","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2013-05-16","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}