- 作者：Bernd Schmeck ; Wiebke Beermann ; Vincent van Laak ; Bastian Opitz ; Andreas C. Hocke ; Karolin Meixenberger ; Julia Eitel ; Trinad Chakraborty ; Gudula Schmidt ; Holger Barth ; et al.
- 关键词：Rac1 ; Listeria ; Histones ; Endothelial cells ; Bacterial toxins ; Cytokines
- 刊名：Biochemical Pharmacology
- 出版年：2006
- 期刊代码：2_00062952
- 类别：pha
- 出版时间：30 November 2006
- 卷：72
- 期：11
- 页码：1367-1374
- 文件大小：417 K
L. monocytogenes induced release of distinct CC and CXC, as well as Th1 and Th2 cytokines and growth factors by endothelial cells and activated RhoA and Rac1. Inhibition of Rac1 by inhibitor Nsc23766 reduced cytokine expression, and slightly yet significantly the uptake of bacteria. Blocking of Rho proteins by Clostridium difficile toxin B-10463 (TcdB) reduced Listeria-dependent cytokine expression, whereas activating Rho proteins by Escherichia coli CNF1 increased it. We analyzed regulation of IL-8 expression in more detail: Listeria-induced IL-8 release was reduced by inhibition of RhoA, Rac1 and Cdc42 (TcdB) or Rac1 while blocking of RhoA/B/C by Clostridium limosum C3 fusion toxin (C3FT) or Rho kinase by Y27632 reduced cytokine expression only slightly. Activation of RhoA, Rac1 and Cdc42 (CNF1), but not of RhoA alone (CNFY), enhanced Listeria-dependent IL-8 release significantly. Furthermore, inhibition of RhoA, Rac1 and Cdc42 (TcdB) and Rac1 (Nsc23766), but not of RhoA (C3FT) reduced Listeria-related recruitment of NF-κB/p65 and RNA polymerase II to the il8 promoter, as well as acetylation of histone H4 and Ser10/Lys14-phosphorylation/acetylation of histone H3 at the il8 gene promoter in HUVEC.
In conclusion, Rac1 contributed to L. monocytogenes-induced cytokine expression by human endothelial cells.