{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T02:09:54Z","timestamp":1771466994138,"version":"3.50.1"},"reference-count":50,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2015,11,1]],"date-time":"2015-11-01T00:00:00Z","timestamp":1446336000000},"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":[[2015,11,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Asthma is characterized by a T helper type 2 phenotype and by chronic allergen-induced airway inflammation (AAI). Environmental exposure to air pollution ultrafine particles (i.e., nanoparticles) exacerbates AAI, and a concern is possible exacerbation posed by engineered nanoparticles generated by emerging nanotechnologies. Signal transducer and activator of transcription (STAT) 1 is a transcription factor that maintains T helper type 1 cell development. However, the role of STAT1 in regulating AAI or exacerbation by nanoparticles has not been explored. In this study, mice with whole-body knockout of the Stat1 gene (Stat1\u2212\/\u2212) or wild-type (WT) mice were sensitized to ovalbumin (OVA) allergen and then exposed to multiwalled carbon nanotubes (MWCNTs) by oropharygneal aspiration. In Stat1\u2212\/\u2212 and WT mice, OVA increased eosinophils in bronchoalveolar lavage fluid, whereas MWCNTs increased neutrophils. Interestingly, OVA sensitization prevented MWCNT-induced neutrophilia and caused only eosinophilic inflammation. Stat1\u2212\/\u2212 mice displayed increased IL-13 in bronchoalveolar lavage fluid at 1 day compared with WT mice after treatment with OVA or OVA and MWCNTs. At 21 days, the lungs of OVA-sensitized Stat1\u2212\/\u2212 mice displayed increased eosinophilia, goblet cell hyperplasia, airway fibrosis, and subepithelial apoptosis. MWCNTs further increased OVA-induced goblet cell hyperplasia, airway fibrosis, and apoptosis in Stat1\u2212\/\u2212 mice at 21 days. These changes corresponded to increased levels of profibrogenic mediators (transforming growth factor-\u03b21, TNF-\u03b1, osteopontin) but decreased IL-10 in Stat1\u2212\/\u2212 mice. Finally, fibroblasts isolated from the lungs of Stat1\u2212\/\u2212 mice produced significantly more collagen mRNA and protein in response to transforming growth factor-\u03b21 compared with WT lung fibroblasts. Our results support a protective role for STAT1 in chronic AAI and exacerbation of remodeling caused by MWCNTs.<\/jats:p>","DOI":"10.1165\/rcmb.2014-0221oc","type":"journal-article","created":{"date-parts":[[2015,3,25]],"date-time":"2015-03-25T13:02:09Z","timestamp":1427288529000},"page":"625-636","source":"Crossref","is-referenced-by-count":37,"title":["Role of Signal Transducer and Activator of Transcription 1 in Murine Allergen\u2013Induced Airway Remodeling and Exacerbation by Carbon Nanotubes"],"prefix":"10.1093","volume":"53","author":[{"given":"Elizabeth A.","family":"Thompson","sequence":"first","affiliation":[{"name":"Environmental and Molecular Toxicology Program, Department of Biological Sciences, North Carolina State University, Raleigh, North Carolina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brian C.","family":"Sayers","sequence":"additional","affiliation":[{"name":"Environmental and Molecular Toxicology Program, Department of Biological Sciences, North Carolina State University, Raleigh, North Carolina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ellen E.","family":"Glista-Baker","sequence":"additional","affiliation":[{"name":"Environmental and Molecular Toxicology Program, Department of Biological Sciences, North Carolina State University, Raleigh, North Carolina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kelly A.","family":"Shipkowski","sequence":"additional","affiliation":[{"name":"Environmental and Molecular Toxicology Program, Department of Biological Sciences, North Carolina State University, Raleigh, North Carolina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mark D.","family":"Ihrie","sequence":"additional","affiliation":[{"name":"Environmental and Molecular Toxicology Program, Department of Biological Sciences, North Carolina State University, Raleigh, North Carolina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katherine S.","family":"Duke","sequence":"additional","affiliation":[{"name":"Environmental and Molecular Toxicology Program, Department of Biological Sciences, North Carolina State University, Raleigh, North Carolina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexia J.","family":"Taylor","sequence":"additional","affiliation":[{"name":"Environmental and Molecular Toxicology Program, Department of Biological Sciences, North Carolina State University, Raleigh, North Carolina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James C.","family":"Bonner","sequence":"additional","affiliation":[{"name":"Environmental and Molecular Toxicology Program, Department of Biological Sciences, North Carolina State University, Raleigh, North Carolina"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2015,11,1]]},"reference":[{"key":"2026021122351006700_bib1","first-page":"1","article-title":"Trends in asthma prevalence, health care use, and mortality in the United States, 2001\u20132010","volume":"94","author":"Akinbami","year":"2012","journal-title":"NCHS"},{"key":"2026021122351006700_bib2","doi-asserted-by":"crossref","first-page":"B2","DOI":"10.1038\/35037000","article-title":"The epidemic of allergy and asthma","volume":"402","author":"Holgate","year":"1999","journal-title":"Nature"},{"key":"2026021122351006700_bib3","doi-asserted-by":"crossref","first-page":"447S","DOI":"10.1378\/chest.123.3_suppl.447S","article-title":"Asthma and the human genome project: summary of the 45th Annual Thomas L. 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