{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T23:47:40Z","timestamp":1791503260246,"version":"4.3.4"},"reference-count":94,"publisher":"American Physiological Society","issue":"7","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Cell Physiology"],"published-print":{"date-parts":[[2012,4,1]]},"abstract":"<jats:p> Lipoxins are formed by leukocytes during cell-cell interactions with epithelial or endothelial cells. Native lipoxin A<jats:sub>4<\/jats:sub> (LXA<jats:sub>4<\/jats:sub>) binds to the G protein-coupled lipoxin receptors formyl peptide receptor 2 (FPR2)\/ALX and CysLT1. Furthermore, LXA<jats:sub>4<\/jats:sub> inhibits recruitment of neutrophils, by attenuating chemotaxis, adhesion, and transmigration across vascular endothelial cells. LXA<jats:sub>4<\/jats:sub> thus appears to serve as an endogenous \u201cstop signal\u201d for immune cell-mediated tissue injury (Serhan CN; Annu Rev Immunol 25: 101\u2013137, 2007). The role of LXA<jats:sub>4<\/jats:sub> has not been addressed in salivary epithelium, and little is known about its effects on vascular endothelium. Here, we determined that interleukin-1\u03b2 (IL-1\u03b2) and tumor necrosis factor-\u03b1 (TNF-\u03b1) receptor activation in vascular endothelium and salivary epithelium upregulated the expression of adhesion molecules that facilitates the binding of immune cells. We hypothesize that the activation of the ALX\/FPR2 and\/or CysLT1 receptors by LXA<jats:sub>4<\/jats:sub> decreases this cytokine-mediated upregulation of cell adhesion molecules that enhance lymphocyte binding to both the vascular endothelium and salivary epithelium. In agreement with this hypothesis, we observed that nanomolar concentrations of LXA<jats:sub>4<\/jats:sub> blocked IL-1\u03b2- and TNF-\u03b1-mediated upregulation of E-selectin and intercellular cell adhesion molecule-1 (ICAM-1) on human umbilical vein endothelial cells (HUVECs). Binding of Jurkat cells to stimulated HUVECs was abrogated by LXA<jats:sub>4<\/jats:sub>. Furthermore, LXA<jats:sub>4<\/jats:sub> preincubation with human submandibular gland cell line (HSG) also blocked TNF-\u03b1-mediated upregulation of vascular cell adhesion molecule-1 (VCAM-1) in these cells, and it reduced lymphocyte adhesion. These findings suggest that ALX\/FPR2 and\/or CysLT1 receptor activation in endothelial and epithelial cells blocks cytokine-induced adhesion molecule expression and consequent binding of lymphocytes, a critical event in the pathogenesis of Sj\u00f6gren's syndrome (SS). <\/jats:p>","DOI":"10.1152\/ajpcell.00259.2011","type":"journal-article","created":{"date-parts":[[2011,12,29]],"date-time":"2011-12-29T02:56:54Z","timestamp":1325127414000},"page":"C968-C978","source":"Crossref","is-referenced-by-count":29,"title":["Lipoxin A<sub>4<\/sub> inhibits immune cell binding to salivary epithelium and vascular endothelium"],"prefix":"10.1152","volume":"302","author":[{"given":"Sreedevi","family":"Chinthamani","sequence":"first","affiliation":[{"name":"Department of Oral Biology, School of Dental Medicine and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olutayo","family":"Odusanwo","sequence":"additional","affiliation":[{"name":"Department of Oral Biology, School of Dental Medicine and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nandini","family":"Mondal","sequence":"additional","affiliation":[{"name":"Department of Chemical and Biological Engineering, School of Engineering and Applied Sciences, University at Buffalo, The State University of New York, Buffalo, New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joel","family":"Nelson","sequence":"additional","affiliation":[{"name":"Department of Oral Biology, School of Dental Medicine and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sriram","family":"Neelamegham","sequence":"additional","affiliation":[{"name":"Department of Chemical and Biological Engineering, School of Engineering and Applied Sciences, University at Buffalo, The State University of New York, Buffalo, New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olga J.","family":"Baker","sequence":"additional","affiliation":[{"name":"Department of Oral Biology, School of Dental Medicine and"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"24","reference":[{"key":"B1","doi-asserted-by":"crossref","first-page":"203","DOI":"10.4049\/jimmunol.130.1.203","volume":"130","author":"Adamson TC","year":"1983","journal-title":"J Immunol"},{"key":"B2","first-page":"39","volume":"37","author":"Aziz KE","year":"1992","journal-title":"J Clin Lab Immunol"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1006\/clin.1996.0094"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0803175"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00144.2008"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1016\/j.molimm.2007.05.009"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0705912"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.20134"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.2353\/ajpath.2006.051056"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/34.4.326"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1186\/ar2457"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(91)90279-8"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.052533799"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V84.7.2068.2068"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2006-05-020875"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1084\/jem.191.7.1197"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.92.21.9475"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1046\/j.1440-1711.2002.01118.x"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00380.2008"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2249.1996.d01-824.x"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1136\/ard.52.11.806"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1038\/gene.2009.20"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2006.07.010"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1055\/s-0038-1646385"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.300.2.385"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V94.12.4132"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1016\/j.plefa.2005.05.005"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1084\/jem.180.1.253"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V81.12.3395.3395"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0705356"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1933204100"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0404722101"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1016\/S0889-857X(21)00314-8"},{"key":"B35","doi-asserted-by":"crossref","first-page":"5532","DOI":"10.4049\/jimmunol.152.11.5532","volume":"152","author":"Fox RI","year":"1994","journal-title":"J Immunol"},{"key":"B36","doi-asserted-by":"crossref","first-page":"2226","DOI":"10.4049\/jimmunol.163.4.2226","volume":"163","author":"Fujihara T","year":"1999","journal-title":"J Immunol"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.168.10.5260"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.167.5.2772"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1084\/jem.187.8.1285"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M410638200"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1021\/jm030569l"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-3083.1999.00533.x"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1002\/eji.1830231002"},{"key":"B44","doi-asserted-by":"crossref","first-page":"2558","DOI":"10.4049\/jimmunol.156.7.2558","volume":"156","author":"Haraldsen G","year":"1996","journal-title":"J Immunol"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/39.2.142"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2007.03.011"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1016\/S0008-6363(96)00063-6"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2222.2003.01673.x"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.2353\/ajpath.2008.070834"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1034\/j.1601-0825.2002.02846.x"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.202296999"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.3181\/0707-MR-190"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00507.2001"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.109.159046"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.171.9.4886"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.1038\/nm748"},{"key":"B57","doi-asserted-by":"crossref","first-page":"525","DOI":"10.4049\/jimmunol.155.2.525","volume":"155","author":"Ley K","year":"1995","journal-title":"J Immunol"},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.1016\/j.reuma.2009.10.009"},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.1097\/00041433-199810000-00004"},{"key":"B60","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.272.11.6972"},{"key":"B61","doi-asserted-by":"publisher","DOI":"10.1002\/cyto.a.20952"},{"key":"B62","doi-asserted-by":"publisher","DOI":"10.1016\/j.cca.2010.06.019"},{"key":"B63","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2009-07-231480"},{"key":"B64","doi-asserted-by":"publisher","DOI":"10.1096\/fasebj.7.6.8472890"},{"key":"B65","doi-asserted-by":"publisher","DOI":"10.1016\/S0049-0172(96)80034-5"},{"key":"B66","doi-asserted-by":"publisher","DOI":"10.1084\/jem.179.4.1145"},{"key":"B67","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2004.05.003"},{"key":"B67a","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00207.2011"},{"key":"B68","doi-asserted-by":"publisher","DOI":"10.1002\/art.20301"},{"key":"B69","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.04-1494"},{"key":"B70","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V84.8.2749.2749"},{"key":"B71","doi-asserted-by":"publisher","DOI":"10.3109\/08916939209148458"},{"key":"B72","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1005533107"},{"key":"B73","doi-asserted-by":"publisher","DOI":"10.1016\/S0049-0172(95)80025-5"},{"key":"B74","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.ph.57.030195.004043"},{"key":"B75","doi-asserted-by":"publisher","DOI":"10.1002\/jcla.1860070309"},{"key":"B76","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9150(02)00053-9"},{"key":"B77","doi-asserted-by":"publisher","DOI":"10.1007\/s004410050602"},{"key":"B78","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.25.022106.141647"},{"key":"B79","doi-asserted-by":"publisher","DOI":"10.2174\/1568026611109060629"},{"key":"B80","doi-asserted-by":"publisher","DOI":"10.1038\/ni1276"},{"key":"B81","doi-asserted-by":"publisher","DOI":"10.1007\/s100670050109"},{"key":"B82","doi-asserted-by":"publisher","DOI":"10.1016\/j.clim.2008.10.006"},{"key":"B83","doi-asserted-by":"publisher","DOI":"10.1016\/0167-5699(92)90151-V"},{"key":"B84","doi-asserted-by":"publisher","DOI":"10.1002\/1097-0142(19800115)45:2<297::AID-CNCR2820450217>3.0.CO;2-R"},{"key":"B85","doi-asserted-by":"publisher","DOI":"10.1046\/j.1432-1327.2001.02142.x"},{"key":"B86","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.164.5.2660"},{"key":"B87","doi-asserted-by":"publisher","DOI":"10.1038\/346425a0"},{"key":"B88","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(94)90337-9"},{"key":"B89","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780350110"},{"key":"B90","doi-asserted-by":"publisher","DOI":"10.1084\/jem.185.9.1693"},{"key":"B91","first-page":"1884","volume":"29","author":"Tsunawaki S","year":"2002","journal-title":"J Rheumatol"},{"key":"B92","first-page":"1063","volume":"32","author":"Turkcapar N","year":"2005","journal-title":"J Rheumatol"},{"key":"B93","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2249.1999.01037.x"},{"key":"B94","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-3495(02)73956-8"}],"container-title":["American Journal of Physiology-Cell Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.physiology.org\/doi\/pdf\/10.1152\/ajpcell.00259.2011","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,6,17]],"date-time":"2024-06-17T16:52:43Z","timestamp":1718643163000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.physiology.org\/doi\/10.1152\/ajpcell.00259.2011"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,4,1]]},"references-count":94,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2012,4,1]]}},"alternative-id":["10.1152\/ajpcell.00259.2011"],"URL":"https:\/\/doi.org\/10.1152\/ajpcell.00259.2011","relation":{},"ISSN":["0363-6143","1522-1563"],"issn-type":[{"value":"0363-6143","type":"print"},{"value":"1522-1563","type":"electronic"}],"subject":[],"published":{"date-parts":[[2012,4,1]]}}}