Anthocyanins from black soybean seed coats preferentially inhibit TNF-alpha-mediated induction of VCAM-1 over ICAM-1 through the regulation of GATAs and IRF-1.
Adhesion molecules have a key role in pathological inflammation. Thus, we investigated the effect of anthocyanins on the induction of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) by TNF-alpha and the possible molecular mechanisms by which anthocyanins differentially regulate ICAM-1 and VCAM-1 expression. Stimulation of cells with TNF-alpha increased ICAM-1 and VCAM-1 expression, and pretreatment with anthocyanins inhibited VCAM-1 expression, but not ICAM-1 expression. We found that IRF-1 and GATAs, especially GATA-4 and -6, were involved in the TNF-alpha-mediated expression of VCAM-1 but not ICAM-1, and anthocyanins decreased nuclear levels of GATA-4 and GATA-6 as well as IRF-1. Moreover, pretreatment with a Jak/STAT inhibitor decreased TNF-alpha-induced VCAM-1 expression and nuclear GATA-4, GATA-6, and IRF-1 levels. Furthermore, anthocyanins efficiently inhibited the phosphorylation of STAT-3. This suggests that anthocyanins differentially regulate TNF-alpha-mediated expression of VCAM-1 and ICAM-1 through modulation of the GATA and IRF-1 binding activity via Jak/STAT-3 activation.
Nizamutdinova
Irina Tsoy
IT
Department of Pharmacology, School of Medicine and Institute of Health Sciences, Gyeongsang National University, Jinju, Korea.
Kim
Young Min
YM
Chung
Jong Il
JI
Shin
Sung Chul
SC
Jeong
Yong-Kee
YK
Seo
Han Geuk
HG
Lee
Jae Heun
JH
Chang
Ki Churl
KC
Kim
Hye Jung
HJ
D000872:Anthocyanins / Q000494:pharmacology*; D002478:Cells, Cultured; D015536:Down-Regulation; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D050980:GATA Transcription Factors / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics* / Q000378:metabolism; D050856:Interferon Regulatory Factor-1 / Q000235:genetics / Q000378:metabolism*; D010936:Plant Extracts / Q000494:pharmacology; D013025:Glycine max / Q000737:chemistry*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism*; D019010:Vascular Cell Adhesion Molecule-1 / Q000235:genetics* / Q000378:metabolism
D000872:Anthocyanins; D050980:GATA Transcription Factors; C494257:IRF1 protein, human; D050856:Interferon Regulatory Factor-1; D010936:Plant Extracts; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1