{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T04:19:44Z","timestamp":1771474784999,"version":"3.50.1"},"reference-count":58,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2010,9,1]],"date-time":"2010-09-01T00:00:00Z","timestamp":1283299200000},"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":[[2010,9,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>The role of inducible NO synthase (iNOS) in allergic airway inflammation remains elusive. We tested the hypothesis that iNOS plays different roles during acute versus chronic airway inflammation. Acute and chronic mouse models of OVA-induced airway inflammation were used to conduct the study. We showed that iNOS deletion was associated with a reduction in eosinophilia, mucus hypersecretion, and IL-5 and IL-13 production upon the acute protocol. Such protection was completely abolished upon the chronic protocol. Interestingly, pulmonary fibrosis observed in wild-type mice under the chronic protocol was completely absent in iNOS\u2212\/\u2212 mice despite persistent IL-5 and IL-13 production, suggesting that these cytokines were insufficient for pulmonary fibrosis. Such protection was associated with reduced collagen synthesis and indirect but severe TGF-\u03b2 modulation as confirmed using primary lung smooth muscle cells. Although activation of matrix metalloproteinase-2\/-9 exhibited little change, the large tissue inhibitor of metalloproteinase-2 (TIMP-2) increase detected in wild-type mice was absent in the iNOS\u2212\/\u2212 counterparts. The regulatory effect of iNOS on TIMP-2 may be mediated by peroxynitrite, as the latter reversed TIMP-2 expression in iNOS\u2212\/\u2212 lung smooth muscle cells and fibroblasts, suggesting that the iNOS\u2013TIMP-2 link may explain the protective effect of iNOS-knockout against pulmonary fibrosis. Analysis of lung sections from chronically OVA-exposed iNOS\u2212\/\u2212 mice revealed evidence of residual but significant protein nitration, prevalent oxidative DNA damage, and poly(ADP-ribose) polymerase-1 activation. Such tissue damage, inflammatory cell recruitment, and mucus hypersecretion may be associated with substantial arginase expression and activity. The results in this study exemplify the complexity of the role of iNOS in asthma and the preservation of its potential as a therapeutic a target.<\/jats:p>","DOI":"10.4049\/jimmunol.0904214","type":"journal-article","created":{"date-parts":[[2010,7,29]],"date-time":"2010-07-29T02:23:24Z","timestamp":1280370204000},"page":"3076-3085","source":"Crossref","is-referenced-by-count":57,"title":["Requirement for Inducible Nitric Oxide Synthase in Chronic Allergen Exposure-Induced Pulmonary Fibrosis but Not Inflammation"],"prefix":"10.1093","volume":"185","author":[{"given":"Amarjit S","family":"Naura","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Experimental Therapeutics, Louisiana State University Health Sciences Center , New Orleans, LA 70112"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mourad","family":"Zerfaoui","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Experimental Therapeutics, Louisiana State University Health Sciences Center , New Orleans, LA 70112"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hogyoung","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Experimental Therapeutics, Louisiana State University Health Sciences Center , New Orleans, LA 70112"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zakaria Y","family":"Abd Elmageed","sequence":"additional","affiliation":[{"name":"Stanley S. Scott Cancer Center, Louisiana State University Health Sciences Center , New Orleans, LA 70112"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paulo C","family":"Rodriguez","sequence":"additional","affiliation":[{"name":"Stanley S. Scott Cancer Center, Louisiana State University Health Sciences Center , New Orleans, LA 70112"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chetan P","family":"Hans","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Experimental Therapeutics, Louisiana State University Health Sciences Center , New Orleans, LA 70112"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jihang","family":"Ju","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Experimental Therapeutics, Louisiana State University Health Sciences Center , New Orleans, LA 70112"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Youssef","family":"Errami","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Experimental Therapeutics, Louisiana State University Health Sciences Center , New Orleans, LA 70112"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiwon","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Experimental Therapeutics, Louisiana State University Health Sciences Center , New Orleans, LA 70112"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Augusto C","family":"Ochoa","sequence":"additional","affiliation":[{"name":"Stanley S. Scott Cancer Center, Louisiana State University Health Sciences Center , New Orleans, LA 70112"},{"name":"Department of Pediatrics, Louisiana State University Health Sciences Center , New Orleans, LA 70112"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A Hamid","family":"Boulares","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Experimental Therapeutics, Louisiana State University Health Sciences Center , New Orleans, LA 70112"},{"name":"Stanley S. Scott Cancer Center, Louisiana State University Health Sciences Center , New Orleans, LA 70112"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2010,9,1]]},"reference":[{"key":"2025032411503541700_r1","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1183\/09031936.00155307","article-title":"A new perspective on concepts of asthma severity and control","volume":"32","author":"Taylor","year":"2008","journal-title":"Eur. Respir. 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