Induction of heme oxygenase 1 by arsenite inhibits cytokine-induced monocyte adhesion to human endothelial cells.
Heme oxygenase-1 (HO-1) is an oxidative stress responsive gene upregulated by various physiological and exogenous stimuli. Arsenite, as an oxidative stressor, is a potent inducer of HO-1 in human and rodent cells. In this study, we investigated the mechanistic role of arsenite-induced HO-1 in modulating tumor necrosis factor alpha (TNF-alpha) induced monocyte adhesion to human umbilical vein endothelial cells (HUVEC). Arsenite pretreatment, which upregulated HO-1 in a time- and concentration-dependent manner, inhibited TNF-alpha-induced monocyte adhesion to HUVEC and intercellular adhesion molecule 1 protein expression by 50% and 40%, respectively. Importantly, knockdown of HO-1 by small interfering RNA abolished the arsenite-induced inhibitory effects. These results indicate that induction of HO-1 by arsenite inhibits the cytokine-induced monocyte adhesion to HUVEC by suppressing adhesion molecule expression. These findings established an important mechanistic link between the functional monocyte adhesion properties of HUVEC and the induction of HO-1 by arsenite.
College of Pharmacy, MSC09 5360, 1 University of New Mexico, Albuquerque, NM 87131-0001, USA.
Xi
X
Sun
Jingbo
J
Pi
Wenlan
W
Liu
Laurie G
LG
Hudson
Ke Jian
KJ
Liu
Changjian
C
Feng
D018053:Arsenites / Q000633:toxicity*; D002448:Cell Adhesion / Q000187:drug effects; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000502:physiology*; D004790:Enzyme Induction / Q000187:drug effects*; D051547:Heme Oxygenase-1 / Q000378:metabolism*; D006801:Humans; D009000:Monocytes / Q000166:cytology* / Q000502:physiology
D018053:Arsenites; D016207:Cytokines; D051547:Heme Oxygenase-1; C015001:arsenite