{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T23:52:55Z","timestamp":1769644375106,"version":"3.49.0"},"reference-count":55,"publisher":"Oxford University Press (OUP)","issue":"8","license":[{"start":{"date-parts":[[2009,4,1]],"date-time":"2009-04-01T00:00:00Z","timestamp":1238544000000},"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":[[2009,4,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Human rhinovirus (HRV) infections can trigger exacerbations of lower airway diseases. Infection of airway epithelial cells induces production of a number of proinflammatory chemokines that may exacerbate airway inflammation, including CXCL10, a chemoattractant for type 1 lymphocytes and NK cells. Primary human bronchial epithelial cells and the BEAS-2B human bronchial epithelial cell line were used to examine the role of MAPK pathways in HRV-16-induced production of CXCL10. Surprisingly, PD98059 and U0126, two inhibitors of the MEK1\/2-ERK MAPK pathway, significantly enhanced HRV-16-induced CXCL10 mRNA and protein. This enhancement was not seen with IFN-\u03b2-induced production of CXCL10. Studies using small interfering RNA revealed that knockdown of MEK1, but not MEK2, was associated with enhanced HRV-induced CXCL10 production. Promoter construct studies revealed that PD98059 and U0126 enhanced HRV-16-induced transcriptional activation of CXCL10. HRV-16-induced promoter activation was regulated by two NF-\u03baB binding sites, \u03baB1 and \u03baB2, and by an IFN-stimulated response element. Inhibitors of the MEK1\/2-ERK pathway did not alter HRV-16-induced activation of tandem repeat \u03baB1 or \u03baB2 constructs, nor did they alter HRV-16-induced nuclear translocation\/binding of NF-\u03baB to either \u03baB1 or \u03baB2 recognition sequences. Furthermore, PD98059 and U0126 did not alter phosphorylation or degradation of I\u03baB\u03b1. In contrast, inhibitors of the MEK1\/2-ERK pathway, and small interfering RNA knockdown of MEK1, enhanced nuclear translocation\/binding of IFN regulatory factor (IRF)-1 to the IFN-stimulated response element recognition sequence in HRV-16 infected cells. We conclude that activation of MEK1 selectively down-regulates HRV-16-induced expression of CXCL10 via modulation of IRF-1 interactions with the gene promoter in human airway epithelial cells.<\/jats:p>","DOI":"10.4049\/jimmunol.0802401","type":"journal-article","created":{"date-parts":[[2009,4,2]],"date-time":"2009-04-02T16:38:25Z","timestamp":1238690305000},"page":"4854-4864","source":"Crossref","is-referenced-by-count":34,"title":["Selective Transcriptional Down-Regulation of Human Rhinovirus-Induced Production of CXCL10 from Airway Epithelial Cells via the MEK1 Pathway"],"prefix":"10.1093","volume":"182","author":[{"given":"Raza S","family":"Zaheer","sequence":"first","affiliation":[{"name":"Airway Inflammation Group, Institute of Infection, Immunity and Inflammation, University of Calgary , Calgary, Alberta,","place":["Canada"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rommy","family":"Koetzler","sequence":"additional","affiliation":[{"name":"Airway Inflammation Group, Institute of Infection, Immunity and Inflammation, University of Calgary , Calgary, Alberta,","place":["Canada"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Neil S","family":"Holden","sequence":"additional","affiliation":[{"name":"Airway Inflammation Group, Institute of Infection, Immunity and Inflammation, University of Calgary , Calgary, Alberta,","place":["Canada"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shahina","family":"Wiehler","sequence":"additional","affiliation":[{"name":"Airway Inflammation Group, Institute of Infection, Immunity and Inflammation, University of Calgary , Calgary, Alberta,","place":["Canada"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David","family":"Proud","sequence":"additional","affiliation":[{"name":"Airway Inflammation Group, Institute of Infection, Immunity and Inflammation, University of Calgary , Calgary, Alberta,","place":["Canada"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2009,4,15]]},"reference":[{"key":"2026012806165848500_R1","first-page":"1225","article-title":"Community study of role of viral infections in exacerbations of asthma in 9\u201311 year old children.","volume-title":"Br. 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