Macrophage inflammatory protein-1beta induced cell adhesion with increased intracellular reactive oxygen species.

Abstract

UNLABELLED:

To investigate the role of macrophage inflammatory protein-1 beta (MIP-1beta) in the development of atherosclerosis, we designed an in vitro study to elucidate the mechanisms of monocyte-endothelium adhesion via intracellular reactive oxygen species (ROS). Angiotensin II (AngII) was used as a positive control. Furthermore, we examined the efficacy of MIP-1beta as a predictor of stroke and cardiovascular events in hypertensive patients. MIP-1beta or AngII stimulation significantly increased ROS production and adhesion of THP-1 cells to inflamed human umbilical vein endothelial cells. Cell adhesion and ROS production were inhibited in stimulated THP-1 cells by: inhibition of ROS signaling with N-acetylcysteine, diphenyleneiodonium, or PEG-Catalase; inhibition of PI3Kgamma with siRNA or LY294002; and by Rac1 siRNA. The MIP-1 beta or AngII stimulation did not increase surface expression of integrins, very late antigen 4 (VLA-4) and lymphocyte function-associated antigen 1 (LFA-1), but cell adhesion was reduced by using an antiVLA-4 or an antiLFA-1 antibody. Moreover, cell adhesion and ROS production stimulated with MIP-1beta or AngII were completely inhibited by fluvastatin. In our clinical study, patients with the highest quartile of MIP-1beta showed a higher risk of stroke and cardiovascular events by a Cox proportional-hazards model. In conclusion, MIP-1beta directly induced cell adhesion to endothelial cells through oxidative stress via PI3k-Rac1 cascades. Serum MIP-1beta level might be a useful predictor for cerebro-cardiovascular events in hypertensive patients.

CONDENSED ABSTRACT:

We designed an in vitro investigation to examine the role of MIP-1beta on the development of atherosclerosis, including cell adhesion involving CAMs and ROS production, compared with angiotensin II. Furthermore, we investigated the prognostic impact of MIP-1beta on stroke and cardiovascular events in hypertensive patients in a small cohort study.

• Authors: Yuji Tatara, Mitsuru Ohishi, Koichi Yamamoto, Atsushi Shiota, Norihiro Hayashi, Yoshihiro Iwamoto, Masao Takeda, Takashi Takagi, Tomohiro Katsuya, Toshio Ogihara, Hiromi Rakugi
• Journal: Journal of molecular and cellular cardiology (J Mol Cell Cardiol) Vol. 47 Issue 1 Pg. 104-11 (Jul 2009) ISSN: 1095-8584 [Electronic] England
• PMID: 19328808 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Chemokine CCL4
• Chromones
• Enzyme Inhibitors
• Free Radical Scavengers
• Integrin alpha4beta1
• Lymphocyte Function-Associated Antigen-1
• Morpholines
• Onium Compounds
• Phosphoinositide-3 Kinase Inhibitors
• RAC1 protein, human
• Reactive Oxygen Species
• catalase-polyethylene glycol
• 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
• Polyethylene Glycols
• diphenyleneiodonium
• Catalase
• rac1 GTP-Binding Protein
• Acetylcysteine

Topics

• Acetylcysteine (pharmacology)
• Analysis of Variance
• Blotting, Western
• Catalase (pharmacology)
• Cell Adhesion (drug effects)
• Cell Line
• Cell Line, Tumor
• Cerebrovascular Disorders (metabolism)
• Chemokine CCL4 (metabolism, pharmacology)
• Chromones (pharmacology)
• Enzyme Inhibitors (pharmacology)
• Free Radical Scavengers (pharmacology)
• Humans
• Integrin alpha4beta1 (metabolism)
• Lymphocyte Function-Associated Antigen-1 (metabolism)
• Models, Biological
• Morpholines (pharmacology)
• Onium Compounds (pharmacology)
• Phosphatidylinositol 3-Kinases (genetics, metabolism)
• Phosphoinositide-3 Kinase Inhibitors
• Polyethylene Glycols (pharmacology)
• RNA Interference
• Reactive Oxygen Species (metabolism)
• rac1 GTP-Binding Protein (genetics, metabolism)