Tanshinone IIA inhibits TNF-alpha-mediated induction of VCAM-1 but not ICAM-1 through the regulation of GATA-6 and IRF-1
- Authors
- Nizamutdinova, Irina Tsoy; Kim, Young Min; Jin, Hana; Son, Kun Ho; Lee, Jae Heun; Chang, Ki Churl; Kim, Hye Jung
- Issue Date
- Dec-2012
- Publisher
- ELSEVIER
- Keywords
- Tanshinone IIA; VCAM-1; ICAM-1; GATA; IRF-1
- Citation
- INTERNATIONAL IMMUNOPHARMACOLOGY, v.14, no.4, pp.650 - 657
- Indexed
- SCIE
SCOPUS
- Journal Title
- INTERNATIONAL IMMUNOPHARMACOLOGY
- Volume
- 14
- Number
- 4
- Start Page
- 650
- End Page
- 657
- URI
- https://scholarworks.bwise.kr/gnu/handle/sw.gnu/21885
- DOI
- 10.1016/j.intimp.2012.09.017
- ISSN
- 1567-5769
- Abstract
- The goal of this study was to investigate the differential effect of tanshinone IIA 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 it regulates ICAM-1 and VCAM-1 expression differentially. Stimulation of human umbilical vein endothelial cells (HUVEC) with TNF-alpha increased ICAM-1 and VCAM-1 expressions, and the pretreatment with tanshinone IIA concentration dependently inhibited VCAM-1 expression but not ICAM-1 expression. In previous study, PI3K/Akt, PKC and Jak/STAT-3 pathways were involved in the INF-alpha-mediated induction of VCAM-1 but not ICAM-1. Thus, we examined the effect of tanshinone IIA on INF-alpha-mediated activations of PI3K/Akt, PKC and Jak/STAT-3 pathways. Tanshinone IIA efficiently inhibited the phosphorylations of Akt, PKC and STAT-3 by TNF-alpha. Moreover, we determined the effect of tanshinone IIA on IRF-1 or GATAs induction and binding activity to VCAM-1 promoter since the upstream promoter region of VCAM-1 but not ICAM-1 contains IRF-1 and GATA binding motifs. Western blot analysis and ChIP assay showed that tanshinone IIA efficiently inhibited TNF-alpha-increased nuclear level of IRF-1 and GATA-6 and their binding affinity to VCAM-1 promoter region. Taken together, tanshinone IIA selectively inhibits TNF-alpha-mediated expression of VCAM-1 but not ICAM-1 through modulation of PI3/Akt, PKC and Jak/STAT-3 pathway as well as IRF-1 and GATA-6 binding activity. (C) 2012 Elsevier B.V. All rights reserved.
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