{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T13:53:45Z","timestamp":1791122025429,"version":"4.1.0"},"reference-count":62,"publisher":"Oxford University Press (OUP)","issue":"11","license":[{"start":{"date-parts":[[2005,12,1]],"date-time":"2005-12-01T00:00:00Z","timestamp":1133395200000},"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":[[2005,12,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Previously, we elucidated the intracellular mechanisms by which neutrophil elastase (NE) up-regulates inflammatory gene expression in bronchial epithelial cells. In this study, we examine the effects of both IL-1 and NE on inflammatory gene expression in 16HBE14o\u2212 bronchial epithelial cells and investigate approaches to abrogate these inflammatory responses. IL-1 induced IL-8 protein production in time- and dose-dependent fashions, an important observation given that IL-8 is a potent neutrophil chemoattractant and a key inflammatory mediator. IL-1 and NE were shown to activate the p38 MAPK pathway in 16HBE14o\u2212 cells. Western blot analysis demonstrated IL-1R-associated kinase 1 (IRAK-1) degradation in response to stimulation with both IL-1 and NE. In addition, the expression of dominant negative IRAK-1 (IRAK-1\u0394), IRAK-2\u0394, or IRAK-4\u0394 inhibited IL-1- and NE-induced NF-\u03baB-linked reporter gene expression. Dominant negative versions of the intracellular adaptor proteins MyD88 (MyD88\u0394) and MyD88 adaptor-like (Mal P\/H) abrogated NE-induced NF-\u03baB reporter gene expression. In contrast, only MyD88\u0394 was found to inhibit IL-1-induced NF-\u03baB reporter activity. We also investigated the vaccinia virus proteins, A46R and A52R, which have been shown to antagonize IL-1 signaling. Transfection with A46R or A52R cDNA inhibited IL-1- and NE-induced NF-\u03baB and IL-8R gene expression and IL-8 protein production in primary and transformed bronchial epithelial cells. Furthermore, cytokine array studies demonstrated that IL-1 and NE can up-regulate the expression of IL-6, oncostatin M, epithelial cell-derived neutrophil activating peptide-78, growth-related oncogene family members, vascular endothelial growth factor, and GM-CSF, with induction of these proteins inhibited by the viral proteins. These findings identify vaccinia virus proteins as possible therapeutic agents for the manifestations of several inflammatory lung diseases.<\/jats:p>","DOI":"10.4049\/jimmunol.175.11.7594","type":"journal-article","created":{"date-parts":[[2014,4,21]],"date-time":"2014-04-21T01:05:46Z","timestamp":1398042346000},"page":"7594-7601","source":"Crossref","is-referenced-by-count":26,"title":["Viral Inhibition of IL-1- and Neutrophil Elastase-Induced Inflammatory Responses in Bronchial Epithelial Cells"],"prefix":"10.1093","volume":"175","author":[{"given":"Toma\u0301s P","family":"Carroll","sequence":"first","affiliation":[{"name":"Respiratory Research Division, Royal College of Surgeons in Ireland, Education and Research Center, Beaumont Hospital , Dublin ,","place":["Ireland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine M","family":"Greene","sequence":"additional","affiliation":[{"name":"Respiratory Research Division, Royal College of Surgeons in Ireland, Education and Research Center, Beaumont Hospital , Dublin ,","place":["Ireland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clifford C","family":"Taggart","sequence":"additional","affiliation":[{"name":"Respiratory Research Division, Royal College of Surgeons in Ireland, Education and Research Center, Beaumont Hospital , Dublin ,","place":["Ireland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew G","family":"Bowie","sequence":"additional","affiliation":[{"name":"Viral Immune Evasion Group, Department of Biochemistry, Trinity College , Dublin ,","place":["Ireland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shane J","family":"O\u2019Neill","sequence":"additional","affiliation":[{"name":"Respiratory Research Division, Royal College of Surgeons in Ireland, Education and Research Center, Beaumont Hospital , Dublin ,","place":["Ireland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noel G","family":"McElvaney","sequence":"additional","affiliation":[{"name":"Respiratory Research Division, Royal College of Surgeons in Ireland, Education and Research Center, Beaumont Hospital , Dublin ,","place":["Ireland"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2005,12,1]]},"reference":[{"key":"2025032706023890900_R1","first-page":"365","volume-title":"Dis.","year":"1990"},{"key":"2025032706023890900_R2","first-page":"2095","volume-title":"Blood","year":"1996"},{"key":"2025032706023890900_R3","first-page":"443","volume-title":"Nature","year":"1996"},{"key":"2025032706023890900_R4","first-page":"1128","volume-title":"Science","year":"1996"},{"key":"2025032706023890900_R5","first-page":"13757","volume-title":"Chem.","year":"1995"},{"key":"2025032706023890900_R6","first-page":"2097","volume-title":"J. 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