Document Detail

Impaired IL-4 phosphorylation of STAT6 in EBV transformed B-cells.
MedLine Citation:
PMID:  19540524     Owner:  NLM     Status:  MEDLINE    
BACKGROUND: The Interleukin-4 signal transducer and activator of transcription 6 (IL-4-STAT6) signaling pathway plays a pivotal role in regulation of gene transcription. We have previously identified a defective STAT6 activational phenotype in response to IL-4 in patients from our familial Inflammatory Bowel Disease registry. This has been termed Stat6(null) and Stat6(high) is the normal phenotype. The purpose of this study was to investigate the defect in Stat6 activation in Stat6(null) cells.
METHODS: Stat6(null) and Stat6(high) Epstein Barr virus transformed cell lines were stimulated with 10 ng/mL of IL-4 for 0, 10, 30, or 60 min and cytoplasmic and nuclear proteins harvested. Western blot for STAT6, phosphorylated STAT6 (pSTAT6), Janus Kinase (Jak)1 and Jak3 was performed. Cells were also cultured for 48 h and interferon gamma (IFNgamma) measured in the supernatant. Additional cells were cultured with 20 ng/mL of IFNgamma for 90 min or 5 ug of antibody to IFNgamma for 48 h, and then stimulated with IL-4.
RESULTS: There were no differences in cytoplasmic STAT6 in Stat6(null)versus Stat6(high) cells. In Stat6(high) cells, STAT6 was rapidly phosphorylated and translocated to the nucleus. In Stat6(null) cells there was minimal phosphorylation and translocation of pSTAT6 to the nucleus. Spontaneous secretion of IFNgamma by Stat6(null) cells was significantly higher than Stat6(null) cells. Addition of IFNgamma decreased pSTAT6 in Stat6(high) cells to Stat6(null) levels while blocking IFNgamma increased baseline pSTAT6 in Stat6(null) cells to levels similar to Stat6(high) cells.
CONCLUSION: This suggests that the spontaneously produced IFNgamma in the Stat6(null) cell lines suppresses STAT6 function and creates the Stat6(null) phenotype.
Lisa S Poritz; Wen Jie Zhang; Jennifer Thompson; Morgan Boyer; Clarence Clark; Walter A Koltun
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Publication Detail:
Type:  Journal Article     Date:  2009-01-27
Journal Detail:
Title:  The Journal of surgical research     Volume:  162     ISSN:  1095-8673     ISO Abbreviation:  J. Surg. Res.     Publication Date:  2010 Aug 
Date Detail:
Created Date:  2010-07-23     Completed Date:  2010-09-13     Revised Date:  2012-06-05    
Medline Journal Info:
Nlm Unique ID:  0376340     Medline TA:  J Surg Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  290-8     Citation Subset:  IM    
Copyright Information:
Copyright 2010 Elsevier Inc. All rights reserved.
Department of Surgery, The Milton S. Hershey Medical Center, Pennsylvania State University, Hershey, Pennsylvania 17033, USA.
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MeSH Terms
B-Lymphocytes / drug effects,  physiology*,  virology
Blotting, Western
Cell Line
Cell Line, Transformed
Herpesvirus 4, Human / physiology*
Interferon-gamma / pharmacology
Interleukin-4 / metabolism*,  pharmacology
Janus Kinase 1 / metabolism
Janus Kinase 3 / metabolism
Lymphocytes / drug effects,  physiology*
Receptors, Interleukin-4 / physiology*
STAT6 Transcription Factor / deficiency,  metabolism*
Reg. No./Substance:
0/Receptors, Interleukin-4; 0/STAT6 Transcription Factor; 0/STAT6 protein, human; 207137-56-2/Interleukin-4; 82115-62-6/Interferon-gamma; EC protein, human; EC Kinase 1; EC Kinase 3

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