{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T04:32:10Z","timestamp":1772166730549,"version":"3.50.1"},"reference-count":27,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2011,2,1]],"date-time":"2011-02-01T00:00:00Z","timestamp":1296518400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"VA Merit Review Awards"},{"DOI":"10.13039\/100000980","name":"Arthritis Foundation Research Awards","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000980","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2011,2,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>IL-4\u03b42 is a natural splice variant of IL-4 that lacks the region encoded by the second exon. Numerous reports have suggested that the expression levels of IL-4\u03b42 change in various diseases, especially those with pulmonary involvement, but the in vivo effects of this splice variant have never been studied. Replication-deficient, AdV-mediated gene delivery of mIL-4\u03b42 to mouse lungs in vivo was used, and the effects compared with similar adenoviral delivery of mIL-4 or with infection with a noncoding NULL viral construct. Overexpression of IL-4\u03b42 or IL-4 caused pulmonary infiltration by T and B lymphocytes, whereas in contrast to IL-4, IL-4\u03b42 did not induce eosinophilia or goblet cell hyperplasia. Microarray analysis of global gene expression revealed that IL-4\u03b42 and IL-4 had differential effects on gene expression. These splice variants also differentially regulated pulmonary levels of the cytokines TNF-\u03b1, eotaxin, IL-1\u03b1, IFN-\u03b3, and MCP-1, whereas both tended to increase total lung collagen modestly. Pulmonary infiltration by lymphocytes in response to overexpression of IL-4\u03b42 was attenuated but not abrogated completely by germline deficiency of IL-4R\u03b1 or STAT6, whereas deficiency of endogenous IL-4 had no effect. Thus, IL-4\u03b42 promotes lymphocytic inflammation in vivo (although differentially from IL-4, in part), and the effects of IL-4\u03b42 are not mediated by endogenous IL-4. Differential targeting of IL-4\u03b42 and IL-4 may therefore be considered in developing future therapeutic agents.<\/jats:p>","DOI":"10.1189\/jlb.0510271","type":"journal-article","created":{"date-parts":[[2011,2,1]],"date-time":"2011-02-01T23:20:34Z","timestamp":1296602434000},"page":"763-770","source":"Crossref","is-referenced-by-count":24,"title":["Alternatively spliced variants of interleukin-4 promote inflammation differentially"],"prefix":"10.1093","volume":"89","author":[{"given":"Irina G","family":"Luzina","sequence":"first","affiliation":[{"name":"Department of Medicine, University of Maryland School of Medicine , Baltimore, Maryland, USA"},{"name":"Baltimore VA Medical Center , Baltimore, Maryland, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Virginia","family":"Lockatell","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Maryland School of Medicine , Baltimore, Maryland, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nevins W","family":"Todd","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Maryland School of Medicine , Baltimore, Maryland, USA"},{"name":"Baltimore VA Medical Center , Baltimore, Maryland, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kendrick","family":"Highsmith","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Maryland School of Medicine , Baltimore, Maryland, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Achsah D","family":"Keegan","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Maryland School of Medicine , Baltimore, Maryland, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeffrey D","family":"Hasday","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Maryland School of Medicine , Baltimore, Maryland, USA"},{"name":"Baltimore VA Medical Center , Baltimore, Maryland, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sergei P","family":"Atamas","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Maryland School of Medicine , Baltimore, Maryland, USA"},{"name":"Baltimore VA Medical Center , Baltimore, Maryland, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2011,2,1]]},"reference":[{"key":"2023032914005016800_","doi-asserted-by":"crossref","first-page":"701","DOI":"10.1146\/annurev.immunol.17.1.701","article-title":"The IL-4 receptor: signaling mechanisms and biologic functions","volume":"17","author":"Nelms","year":"1999","journal-title":"Annu. 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