Effect of atorvastatin on PM10-induced cytokine production by human alveolar macrophages and bronchial epithelial cells.
Exposure to ambient air pollution particles (PM(10)) has been associated with increased cardiovascular morbidity and mortality. Inhaled pollutants induce a pulmonary and systemic inflammatory response that is thought to exacerbate cardiovascular disease. The 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) have been shown to have anti-inflammatory effects that could contribute to their beneficial effect in cardiovascular disease. The aim of this study is to determine the effects of statins on PM(10)-induced cytokine production in human bronchial epithelial cells (HBECs) and alveolar macrophages (AMs). Primary HBECs and AMs are obtained from resected human lung. Cells are pretreated with different concentrations of atorvastatin for 24 hours and then exposed to 100 microg/mL urban air pollution particles (EHC-93). Cytokine levels (interleukin-1beta, interleukin-8, granulocyte-macrophage colony-stimulating factor, interleukin-6, and tumor necrosis factor-alpha) are measured at messenger RNA and protein levels using real-time polymerase chain reaction and bead-based multiplex immunoassay, respectively. PM(10) exposure increases production of these cytokines by both cell types. Atorvastatin attenuates PM(10)-induced messenger RNA expression and cytokine production by AMs but not by HBECs. It is concluded that statins can modulate the PM(10)-induced inflammatory response in the lung by reducing mediator production by AMs.
Sakamoto
Noriho
N
University of British Columbia and St. Paul's Hospital, Vancouver, British Columbia, Canada.
Hayashi
Shizu
S
Mukae
Hiroshi
H
Vincent
Renaud
R
Hogg
James C
JC
van Eeden
Stephan F
SF
D000368:Aged; D000069059:Atorvastatin; D001980:Bronchi / Q000166:cytology; D002478:Cells, Cultured; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D004336:Drug Antagonism; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D006538:Heptanoic Acids / Q000494:pharmacology*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D016676:Macrophages, Alveolar / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D052638:Particulate Matter / Q000633:toxicity*; D011758:Pyrroles / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D020545:Respiratory Mucosa / Q000187:drug effects* / Q000378:metabolism
D016207:Cytokines; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D052638:Particulate Matter; D011758:Pyrroles; D012333:RNA, Messenger; D000069059:Atorvastatin