AUTHOR=Yeh Hsin-Yu , Hung Shou-Hung , Chen Su-Chiu , Guo Fei-Ran , Huang Hsien-Liang , Peng Jen-Kuei , Lee Chung-Sheng , Tsai Jaw-Shiun 

TITLE=The Expression of Toll-Like Receptor 4 mRNA in PBMCs Is Upregulated in Smokers and Decreases Upon Smoking Cessation

JOURNAL=Frontiers in Immunology

VOLUME=12

YEAR=2021

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2021.667460

DOI=10.3389/fimmu.2021.667460

ISSN=1664-3224

ABSTRACT=<sec><title>Background</title><p>Studies have shown <italic>in vitro</italic> that cigarette smoke condensate stimulates monocytes to express toll-like receptor 4 (TLR4), tumor necrosis factor-α (TNF-α), and intercellular adhesion molecule 1 (ICAM-1), and enhances their adhesion to the endothelium. However, the same effects of cigarette smoking have not been explored <italic>in vivo</italic>. This study is to investigate the effect of cigarette smoking and smoking cessation on their mRNA expression in human peripheral blood mononuclear cells (PBMCs).</p></sec><sec><title>Methods</title><p>A group of 97 smokers and 62 nonsmokers were enrolled. The RNA from PBMCs was assessed with real-time polymerase chain reaction (PCR) to determine the levels of ICAM-1, TNF-α, and TLR4. The same markers in PBMCs of 87 quitters were examined before and at one week, one month, and two months after smoking cessation.</p></sec><sec><title>Results</title><p>Of the 97 smokers, 85 (87.6%) were males, and 30 (48.4%) of the nonsmokers were males (<italic>p</italic> &lt; 0.0001). The mean (SD) age of the smokers was 43.24 (10.89) years, which was younger than 43.45 (11.41) years of nonsmokers (<italic>p</italic> &lt; 0.0001). The incidence of cardiovascular diseases was 13.4% in smokers, which was higher than 1.6% in nonsmokers (<italic>p</italic> &lt; 0.05). Both ICAM-1 and TNF-α mRNA levels in PBMCs were higher among the smokers (<italic>p</italic> &lt; 0.0001). In addition, TLR4 mRNA levels in PBMCs were statistically elevated in the smokers (<italic>p</italic> &lt; 0.0001) comparing with those in the nonsmokers. The mRNA levels of TLR4 and TNF-α in PBMCs decreased in those who had quit smoking for 2 months (<italic>p</italic> &lt; 0.0001).</p></sec><sec><title>Conclusions</title><p>ICAM-1, TNF-α, and TLR4 mRNA expression levels in PBMCs increased in smokers and decreased after being on a smoking cessation program for 2 months. This finding suggested that TLR4 expression may mediate the atherogenic inflammatory process induced by smoking.</p></sec>