| Molecular Mechanism of Interleukin-2-induced Mucosal Homeostasis. | |
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MedLine Citation:
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PMID: 22116305 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Sustained damage to the mucosal lining in patients with Inflammatory Bowel Disease (IBD) facilitates translocation of intestinal microbes to sub-mucosal immune cells leading to chronic inflammation. Previously we demonstrated the role of Jak3 in IL-2-induced IEC migration, one of the early events during intestinal wound repair. In this report we demonstrate that IL-2 also plays a role in IEC homeostasis through concentration-dependent regulation of IEC proliferation and cell-death. At lower concentrations (≤ 50U/ml) IL-2 promoted proliferation, while at higher concentrations (100 U/ml), it promoted apoptosis. Activation by IL-2 led to tyrosine phosphorylation-dependent interactions between Jak3 and p52ShcA only at lower concentrations. Phosphatase SHP1 dephosphorylated IL-2-induced phosphorylated p52ShcA. Higher concentrations of IL-2 decreased the phosphorylation of Jak3 and p52ShcA, disrupted their interactions, redistributed Jak3 to the nucleus, and induced apoptosis in IEC. IL-2 also induced dose dependent up-regulation of p52shcA, and down-regulation of jak3-mRNA. Constitutive over-expression and mir-shRNA mediated knock-down studies showed that expression of both Jak3 and p52ShcA were necessary for IL-2-induced proliferation of IEC. Doxycycline regulated sh-RNA-expression demonstrated that IL-2-induced down regulation of jak3-mRNA was responsible for higher IL-2-induced apoptosis in IEC. Collectively, these data demonstrate a novel mechanism of IL-2-induced mucosal homeostasis through post-translational and transcriptional regulation of Jak3 and p52ShcA. |
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Authors:
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Jayshree Mishra; Christopher M Waters; Narendra Kumar |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-11-23 |
Journal Detail:
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Title: American journal of physiology. Cell physiology Volume: - ISSN: 1522-1563 ISO Abbreviation: - Publication Date: 2011 Nov |
Date Detail:
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Created Date: 2011-11-25 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 100901225 Medline TA: Am J Physiol Cell Physiol Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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Texas A&M Health Sciences Center. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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