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JNK Negatively Regulates Adhesion of Monocytes to Human Endothelial Cells through VCAM‐1
Author(s) -
Nizamutdinova Irina Tsoy,
Chang Ki Churl,
Kim Hye Jung
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.lb670
Subject(s) - vcam 1 , transfection , chromatin immunoprecipitation , gata6 , tumor necrosis factor alpha , microbiology and biotechnology , chemistry , cell adhesion , biology , cell adhesion molecule , transcription factor , icam 1 , promoter , adhesion , immunology , gene expression , biochemistry , gene , organic chemistry
TNF‐α increased VCAM‐1 expression in endothelial cells (EC) and induced adhesion of monocytes and cancer cells to EC. VCAM‐1 siRNA showed significant reduction in the adherent monocytes or cancer cells by TNF‐α. We investigated the mechanisms that regulate VCAM‐1 expression. We found that JNK inhibitor (SP600125) up‐regulated VCAM‐1 increased by TNF‐α. Transfection with dominant negative (DN) JNK1 plasmid resulted in increase of VCAM‐1, whereas JNK1‐overexpressing (OE) vector resulted in inhibition of VCAM‐1 expression, suggesting that JNK negatively regulates VCAM‐1 expression. We tested whether JNK signaling affects IRF‐1 and/or GATA6, which are transcription factors that mediate TNF‐α induction of VCAM‐1 but not ICAM‐1. The DN‐JNK1 enhanced TNF‐α up‐regulation of IRF‐1 whereas JNK1‐OE displayed down‐regulation; but, neither DN‐JNK1 nor JNK1‐OE affected GATA6 level. Chromatin immunoprecipitation assay confirmed that the DN‐JNK1 transfection increases the binding of IRF‐1 to the VCAM‐1 promoter whereas JNK1‐OE inhibits IRF‐1 binding to the VCAM‐1 promoter, but didn't have effect on GATA6. Finally we found that MKP‐7, a negative regulator of JNK was involved in the TNF‐α‐mediated VCAM‐1 expression.