Inhibition of monocyte chemoattractant protein-1 by Krüppel-like factor 5 small interfering RNA in the tumor necrosis factor- alpha-activated human umbilical vein endothelial cells.
Krüppel-like factor 5 (KLF5) is one of the pivotal transcriptional factors communicating with inflammatory cytokines. Regulation of monocyte chemoattractant protein-1 (MCP-1) is a target to prevent from inflammation and atherogenic changes in patient with diabetes mellitus. This study was made to determine whether KLF5 may associate with MCP-1 expression in human umbilical vein endothelial cells (HUVECs) induced by tumor necrosis factor-alpha (TNF-alpha), in terms of the initial events of damaged vascular cells in diabetes. MCP-1 expression was markedly augmented by the treatment of TNF-alpha to HUVECs, but this augmentation was inhibited by KLF5 small interfering RNA, which primarily suppressed the expression of KLF5 at mRNA levels in the cells. Though TNF-alpha augmented the levels of endothelin-1 (ET-1) and attenuated those of embryonic form of myosin heavy chain (SMemb) in HUVECs, the inhibition of KLF5 did not affect the levels of these cytokines in the cells. These results suggested that in HUVECs, KLF5 is playing a critical role in regulating the expression of MCP-1, which has been considered to be involved in the diabetic atherogenic events.
Kumekawa
Mari
M
Third Department of Internal Medicine, Tokyo Medical University, Tokyo, Japan.
Fukuda
Gen
G
Shimizu
Saiko
S
Konno
Kazushige
K
Odawara
Masato
M
D015153:Blotting, Western; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000037:antagonists & inhibitors*; D017077:Culture Media, Conditioned; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism*; D019332:Endothelin-1 / Q000494:pharmacology; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D051741:Kruppel-Like Transcription Factors / Q000235:genetics*; D012313:RNA / Q000096:biosynthesis / Q000302:isolation & purification; D034741:RNA, Small Interfering / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D014471:Umbilical Veins / Q000166:cytology / Q000187:drug effects / Q000378:metabolism
D018932:Chemokine CCL2; D017077:Culture Media, Conditioned; D019332:Endothelin-1; C492214:KLF5 protein, human; D051741:Kruppel-Like Transcription Factors; D034741:RNA, Small Interfering; D014409:Tumor Necrosis Factor-alpha; D012313:RNA