{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T18:51:37Z","timestamp":1780339897360,"version":"3.54.1"},"reference-count":50,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2020,7,1]],"date-time":"2020-07-01T00:00:00Z","timestamp":1593561600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":["www.atsjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2020,7,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Diisocyanates are well-recognized causes of asthma. However, sensitized workers frequently lack diisocyanate-specific IgE, which complicates diagnosis and suggests the disease involves IgE-independent mechanisms. We used a mouse model of methylene diphenyl diisocyanate (MDI) asthma to identify biological pathways that may contribute to asthma pathogenesis. MDI sensitization and respiratory tract exposure were performed in Balb\/c, transgenic B-cell (e.g., IgE)-deficient mice and a genetic background (C57BL\/6)-matched strain. Eosinophils in airway fluid were quantitated by flow cytometry. Lung tissue gene expression was assessed using whole-genome mRNA microarrays. Informatic software was used to identify biological pathways affected by respiratory tract exposure and potential targets for disease intervention. Airway eosinophilia and changes (&amp;gt;1.5-fold; P value\u2009&amp;lt;\u20090.05) in expression of 192 genes occurred in all three mouse strains tested, with enrichment in chemokines and a pattern associated with alternatively activated monocytes\/macrophages. CLCA1 (calcium-activated chloride channel regulator 1) was the most upregulated gene transcript (&amp;gt;100-fold) in all exposed mouse lungs versus controls, followed closely by SLC26A4, another transcript involved in Cl\u2212 conductance. Crofelemer, a U.S. Food and Drug Administration\u2013approved Cl\u2212 channel inhibitor, reduced MDI exposure induction of airway eosinophilia, mucus, CLCA1, and other asthma-associated gene transcripts. Expression changes in a core set of genes occurs independent of IgE in a mouse model of chemical-induced airway eosinophilia. In addition to chemokines and alternatively activated monocytes\/macrophages, the data suggest a crucial role for Cl\u2212 channels in diisocyanate asthma pathology and as a possible target for intervention.<\/jats:p>","DOI":"10.1165\/rcmb.2019-0400oc","type":"journal-article","created":{"date-parts":[[2020,2,26]],"date-time":"2020-02-26T15:56:03Z","timestamp":1582732563000},"page":"25-35","update-policy":"https:\/\/doi.org\/10.1164\/crossmarkpolicies","source":"Crossref","is-referenced-by-count":15,"title":["Analysis of Lung Gene Expression Reveals a Role for Cl\u2212 Channels in Diisocyanate-induced Airway Eosinophilia in a Mouse Model of Asthma Pathology"],"prefix":"10.1093","volume":"63","author":[{"given":"Adam V.","family":"Wisnewski","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, Yale University School of Medicine, New Haven, 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