Document Detail

IL-4 Induces Up-regulation of Endothelial Cell Claudin-5 through Activation of FoxO1: Role in Protection from Complement-mediated Injury.
MedLine Citation:
PMID:  24280217     Owner:  NLM     Status:  Publisher    
Injury to endothelial cells (ECs) often results in cell retraction and gap formation. When caused by antigen aggregation or complement this injury can be prevented by pretreatment of the ECs with IL-4, suggesting that IL-4 modifies the intercellular junction. Therefore we investigated the effects of IL-4 on expression of intercellular junction proteins and whether such effects are required for IL-4-induced resistance of ECs against complement-mediated injury. We found that IL-4 induces up-regulation of the junction protein claudin-5 in porcine ECs through activation of Jak/STAT6 and phosphorylation and translocation of FoxO1 from the nucleus to the cytoplasm. Increased claudin-5 expression resulted in increased transmembrane electrical resistance of the endothelial monolayer and participated in IL-4-induced protection of the ECs from complement injury. Down-regulation of FoxO1 using siRNA by itself caused up-regulation of claudin-5 expression and partial protection from cytotoxicity. This protection was enhanced by stimulation with IL-4. We previously reported that increased phospholipid synthesis and mitochondrial protection were required for IL-4-induced resistance of ECs against complement injury and now we demonstrate a contribution of claudin-5 expression in IL-4-induced protection.
Agustin P Dalmasso; Daniel Goldish; Barbara A Benson; Alexander K Tsai; Karen R Wasiluk; Gregory M Vercellotti
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-11-26
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  -     ISSN:  1083-351X     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  2013 Nov 
Date Detail:
Created Date:  2013-11-27     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
University of Minnesota, United States.
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