{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T02:34:41Z","timestamp":1791254081124,"version":"4.1.0"},"reference-count":47,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2007,11,1]],"date-time":"2007-11-01T00:00:00Z","timestamp":1193875200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2007,11,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>The severity of chronic obstructive pulmonary disease correlates with increased numbers of cytotoxic CD8+ T lymphocytes in the lung parenchyma. CD8+ T lymphocytes release IFN-\u03b3 which stimulates airway epithelial cells to produce CXCR3 chemokines leading to further recruitment of CD8+ T lymphocytes. To evaluate the signaling pathways involved in regulation of CXCR3 ligands, the human bronchial epithelial cell line BEAS-2B was stimulated with IFN-\u03b3 and the release of the CXCR3 ligands was measured by ELISA. The release of CXCL9, CXCL10, and CXCL11 was inhibited by an I\u03baB kinase 2 (IKK2) selective inhibitor 2-[(Aminocarbonyl)amino]-5-[4-fluorophenyl]-3-thiophenecarboxamide (TPCA-1) (EC50 values were 0.50 \u00b1 0.03, 0.17 \u00b1 0.06, and 0.45 \u00b1 0.10 \u03bcM, respectively (n = 6)) and an IKK1\/2 selective inhibitor 2-amino-6-(2\u2032cyclopropylemethoxy-6\u2032-hydroxy-phenyl)-4-piperidin-3-yl-pyridine-3-carbonitrile (EC50 values 0.74 \u00b1 0.40, 0.27 \u00b1 0.06, and 0.88 \u00b1 0.29 \u03bcM, respectively (n = 6)). The glucocorticosteroid dexamethasone had no effect on CXCR3 ligand release. The release of CXCL10 was most sensitive to inhibition by IKK2 and a role for IKK2 in CXCL10 release was confirmed by overexpression of dominant-negative adenoviral constructs to IKK2 (68.2 \u00b1 8.3% n = 5), but not of IKK1. Neither phosphorylation of I\u03baB\u03b1, translocation of p65 to the nucleus, or activation of a NF-\u03baB-dependent reporter (Ad-NF-\u03baB-luc) were detected following stimulation of BEAS-2B cells with IFN-\u03b3. These data suggest that IKK2 is also involved in the IFN-\u03b3-stimulated release of the CXCR3 ligands through a novel mechanism that is independent NF-\u03baB.<\/jats:p>","DOI":"10.4049\/jimmunol.179.9.6237","type":"journal-article","created":{"date-parts":[[2014,4,18]],"date-time":"2014-04-18T23:27:18Z","timestamp":1397863638000},"page":"6237-6245","source":"Crossref","is-referenced-by-count":36,"title":["The Role of I\u03baB Kinase 2, but Not Activation of NF-\u03baB, in the Release of CXCR3 Ligands from IFN-\u03b3-Stimulated Human Bronchial Epithelial Cells"],"prefix":"10.1093","volume":"179","author":[{"given":"Susan J","family":"Tudhope","sequence":"first","affiliation":[{"name":"Airway Disease, National Heart and Lung Institute, Imperial College , London ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew C","family":"Catley","sequence":"additional","affiliation":[{"name":"Airway Disease, National Heart and Lung Institute, Imperial College , London ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter S","family":"Fenwick","sequence":"additional","affiliation":[{"name":"Airway Disease, National Heart and Lung Institute, Imperial College , London ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard E K","family":"Russell","sequence":"additional","affiliation":[{"name":"Heatherwood and Wexham Park National Health Service Trust , Berkshire ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William L","family":"Rumsey","sequence":"additional","affiliation":[{"name":"GlaxoSmithKline , Philadelphia, PA 19406"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Newton","sequence":"additional","affiliation":[{"name":"Cell Biology and Anatomy, Respiratory Research Group, University of Calgary , Calgary, Alberta ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter J","family":"Barnes","sequence":"additional","affiliation":[{"name":"Airway Disease, National Heart and Lung Institute, Imperial College , London ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Louise E","family":"Donnelly","sequence":"additional","affiliation":[{"name":"Airway Disease, National Heart and Lung Institute, Imperial College , London ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2007,11,1]]},"reference":[{"key":"2025032723391177700_R1","first-page":"1241","volume-title":"Nat. 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