{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T12:47:34Z","timestamp":1791118054072,"version":"4.1.0"},"reference-count":56,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2004,4,1]],"date-time":"2004-04-01T00:00:00Z","timestamp":1080777600000},"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":[[2004,4,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Intratracheal injection of FITC results in acute lung injury and progresses to fibrosis by day 21 postchallenge. In response to FITC, BALB\/c mice produce IL-4 and IL-13 in the lung. To investigate whether IL-4 and\/or IL-13 were important profibrotic mediators in this model, we examined the fibrotic response to FITC in mice that were genetically deficient in IL-4 (IL-4\u2212\/\u2212), IL-13 (IL-13\u2212\/\u2212), or IL-4 and IL-13 combined (IL-4\/13\u2212\/\u2212). Baseline levels of collagen were similar in all mice. In response to FITC, both BALB\/c and IL-4\u2212\/\u2212 mice developed fibrosis, whereas the IL-13\u2212\/\u2212 and IL-4\/13\u2212\/\u2212 mice were significantly protected, as measured by total lung collagen levels and histology. Total leukocyte recruitment to the lung was similar in all four strains of mice when measured on days 7, 14, and 21 post-FITC. BALB\/c mice showed prominent eosinophilia on day 7 that was absent in IL-4\u2212\/\u2212, IL-13\u2212\/\u2212, and IL-4\/13\u2212\/\u2212 mice, suggesting that eosinophilia is not necessary for development of a fibrotic response. There were no significant differences in the percentages of any other leukocytes analyzed between the genotypes. Similarly, protection in IL-13\u2212\/\u2212 mice was not associated with alterations in cytokine or eicosanoid profiles. Interestingly, TGF-\u03b21 production was not reduced in IL-13\u2212\/\u2212 mice. Analyses of fibroblasts isolated from the four genotypes demonstrated that although there were similar numbers of fibroblasts present in cultures of lung minces, fibroblasts from IL-13-deficient strains have reduced basal and stimulated levels of collagen production. IL-13R\u03b11 expression increases on fibroblasts during fibrotic responses in vivo, and IL-13 increases collagen synthesis in fibroblasts. Thus, IL-13 mediates its profibrotic actions through direct effects on fibroblast production of extracellular matrix.<\/jats:p>","DOI":"10.4049\/jimmunol.172.7.4068","type":"journal-article","created":{"date-parts":[[2014,4,21]],"date-time":"2014-04-21T01:56:20Z","timestamp":1398045380000},"page":"4068-4076","source":"Crossref","is-referenced-by-count":170,"title":["Protection from Fluorescein Isothiocyanate-Induced Fibrosis in IL-13-Deficient, but Not IL-4-Deficient, Mice Results from Impaired Collagen Synthesis by Fibroblasts"],"prefix":"10.1093","volume":"172","author":[{"given":"Jill E","family":"Kolodsick","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, University of Michigan , Ann Arbor, MI 48109"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Galen B","family":"Toews","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, University of Michigan , Ann Arbor, MI 48109"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Jakubzick","sequence":"additional","affiliation":[{"name":"Graduate Program in Immunology, University of Michigan , Ann Arbor, MI 48109"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cory","family":"Hogaboam","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Michigan , Ann Arbor, MI 48109"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas A","family":"Moore","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, University of Michigan , Ann Arbor, MI 48109"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"McKenzie","sequence":"additional","affiliation":[{"name":"Medical Research Council Laboratory of Molecular Biology , Cambridge ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carol A","family":"Wilke","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, University of Michigan , Ann Arbor, MI 48109"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cara J","family":"Chrisman","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, University of Michigan , Ann Arbor, MI 48109"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bethany B","family":"Moore","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, University of Michigan , Ann Arbor, MI 48109"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2004,4,1]]},"reference":[{"key":"2025032708031239500_R1","first-page":"347","volume-title":"Pharmacol. 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