{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T05:30:58Z","timestamp":1791091858846,"version":"4.1.0"},"reference-count":61,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2013,7,1]],"date-time":"2013-07-01T00:00:00Z","timestamp":1372636800000},"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":[[2013,7,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Oxidative stress in allergic asthma may result from oxidase activity or proinflammatory molecules in pollens. Signaling via TLR4 and its adaptor Toll\u2013IL-1R domain\u2013containing adapter inducing IFN-\u03b2 (TRIF) has been implicated in reactive oxygen species\u2013mediated acute lung injury and in Th2 immune responses. We investigated the contributions of oxidative stress and TLR4\/TRIF signaling to experimental asthma induced by birch pollen exposure exclusively via the airways. Mice were exposed to native or heat-inactivated white birch pollen extract (BPEx) intratracheally and injected with the antioxidants, N-acetyl-l-cysteine or dimethylthiourea, prior to sensitization, challenge, or all allergen exposures, to assess the role of oxidative stress and pollen-intrinsic NADPH oxidase activity in allergic sensitization, inflammation, and airway hyperresponsiveness (AHR). Additionally, TLR4 signaling was antagonized concomitantly with allergen exposure, or the development of allergic airway disease was evaluated in TLR4 or TRIF knockout mice. N-acetyl-l-cysteine inhibited BPEx-induced eosinophilic airway inflammation and AHR except when given exclusively during sensitization, whereas dimethylthiourea was inhibitory even when administered with the sensitization alone. Heat inactivation of BPEx had no effect on the development of allergic airway disease. Oxidative stress\u2013mediated AHR was also TLR4 and TRIF independent; however, TLR4 deficiency decreased, whereas TRIF deficiency increased BPEx-induced airway inflammation. In conclusion, oxidative stress plays a significant role in allergic sensitization to pollen via the airway mucosa, but the pollen-intrinsic NADPH oxidase activity and TLR4 or TRIF signaling are unnecessary for the induction of allergic airway disease and AHR. Pollen extract does, however, activate TLR4, thereby enhancing airway inflammation, which is restrained by the TRIF-dependent pathway.<\/jats:p>","DOI":"10.4049\/jimmunol.1103644","type":"journal-article","created":{"date-parts":[[2013,6,18]],"date-time":"2013-06-18T04:50:48Z","timestamp":1371531048000},"page":"922-933","source":"Crossref","is-referenced-by-count":43,"title":["Inhaled Birch Pollen Extract Induces Airway Hyperresponsiveness via Oxidative Stress but Independently of Pollen-Intrinsic NADPH Oxidase Activity, or the TLR4\u2013TRIF Pathway"],"prefix":"10.1093","volume":"191","author":[{"given":"Karim H","family":"Shalaby","sequence":"first","affiliation":[{"name":"Meakins-Christie Laboratories, Research Institute of the McGill University Health Centre, Department of Medicine, McGill University , Montreal, Quebec H2X 2P2,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra","family":"Allard-Coutu","sequence":"additional","affiliation":[{"name":"Meakins-Christie Laboratories, Research Institute of the McGill University Health Centre, Department of Medicine, McGill University , Montreal, Quebec H2X 2P2,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael J","family":"O\u2019Sullivan","sequence":"additional","affiliation":[{"name":"Meakins-Christie Laboratories, Research Institute of the McGill University Health Centre, Department of Medicine, McGill University , Montreal, Quebec H2X 2P2,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily","family":"Nakada","sequence":"additional","affiliation":[{"name":"Meakins-Christie Laboratories, Research Institute of the McGill University Health Centre, Department of Medicine, McGill University , Montreal, Quebec H2X 2P2,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Salman T","family":"Qureshi","sequence":"additional","affiliation":[{"name":"Montreal General Hospital, Research Institute of the McGill University Health Centre, McGill University , Montreal, Quebec H2X 2P2,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian J","family":"Day","sequence":"additional","affiliation":[{"name":"Department of Medicine, National Jewish Health , Denver, CO 80206"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James G","family":"Martin","sequence":"additional","affiliation":[{"name":"Meakins-Christie Laboratories, Research Institute of the McGill University Health Centre, Department of Medicine, McGill University , Montreal, Quebec H2X 2P2,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2013,7,15]]},"reference":[{"key":"2025032405080768300_r1","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1111\/j.1749-6632.2010.05600.x","article-title":"Molecular mechanisms of oxidative stress in airways and lungs with reference to asthma and chronic obstructive pulmonary disease","volume":"1203","author":"Chung","year":"2010","journal-title":"Ann. 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