{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T22:56:21Z","timestamp":1790290581852,"version":"4.1.0"},"reference-count":47,"publisher":"American Physiological Society","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Gastrointestinal and Liver Physiology"],"published-print":{"date-parts":[[2008,11]]},"abstract":"<jats:p>In the intestinal epithelium, activation of phosphatidylinositol 3-kinase (PI3-kinase)\/AKT pathways, via growth factor-mediated signaling, has been shown to regulate cell proliferation and inhibit apoptosis. An immune-activated receptor critical for Th2 immune responses, IL-4R\u03b1 can also activate PI3-kinase via insulin receptor substrate (IRS)-dependent signaling. Here, using the intestinal goblet cell-specific gene RELM\u03b2, we investigated the effect of PI3-kinase activation via Th2 immune responses on the goblet cell phenotype. IL-13 stimulation activated PI3-kinase and AKT signal transduction in LS174T cells. Not only did pharmacological inhibition of PI3-kinase and AKT1\/2 inhibit RELM\u03b2 induction by IL-13, but AKT inhibition also significantly reduced constitutive basal expression of RELM\u03b2, a response reproduced by the simultaneous pharmacological inhibition of both epidermal growth factor receptor and IGF-I receptor signaling. In vivo, the disruption of phosphatase and tensin homolog deleted on chromosome 10 (PTEN), an inhibitor of PI3-kinase activation, led to the activation of RELM\u03b2 expression in the small intestine. Furthermore, induction of an intestinal Th2 immune response by infection with a small intestinal nematode parasite, Heligmosomoides polygyrus, led to enhanced epithelial cell proliferation, activation of AKT as demonstrated by the loss of Foxo1 nuclear localization, and robust induction of RELM\u03b2 expression in wild-type, but not IL-4R\u03b1 knockout, mice. These results demonstrate that Th2 immune responses can regulate goblet cell responses by activation of PI3-kinase and AKT pathways via IL-4R\u03b1.<\/jats:p>","DOI":"10.1152\/ajpgi.90430.2008","type":"journal-article","created":{"date-parts":[[2008,10,3]],"date-time":"2008-10-03T00:25:06Z","timestamp":1222993506000},"page":"G1122-G1130","source":"Crossref","is-referenced-by-count":17,"title":["Immune-mediated signaling in intestinal goblet cells via PI3-kinase- and AKT-dependent pathways"],"prefix":"10.1152","volume":"295","author":[{"given":"Mei-Lun","family":"Wang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sue A.","family":"Keilbaugh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tanesha","family":"Cash-Mason","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xi 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