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

Abstract

BackgroundStudies have shown in vitro 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 in vivo. This study is to investigate the effect of cigarette smoking and smoking cessation on their mRNA expression in human peripheral blood mononuclear cells (PBMCs).MethodsA 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.ResultsOf the 97 smokers, 85 (87.6%) were males, and 30 (48.4%) of the nonsmokers were males (p < 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 (p < 0.0001). The incidence of cardiovascular diseases was 13.4% in smokers, which was higher than 1.6% in nonsmokers (p < 0.05). Both ICAM-1 and TNF-α mRNA levels in PBMCs were higher among the smokers (p < 0.0001). In addition, TLR4 mRNA levels in PBMCs were statistically elevated in the smokers (p < 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 (p < 0.0001).ConclusionsICAM-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.

An integral perspective of canonical cigarette and e-cigarette-related cardiovascular toxicity based on the adverse outcome pathway framework

“…Researchers suggested that cigarette smoke can induce inflammation and promote atherosclerosis via activation of the H1R-TLR2/4-COX2 signaling pathway in HUVECs [133] . Moreover, an epidemiologic study also observed upregulation of TLR4 mRNA in current smokers [134] .…”

Decreased toll-like receptor 4 and CD11b/CD18 expression on peripheral monocytes of hypertensive patients correlates with a lesser extent of endothelial damage: a preliminary study

“…In the present work, males predominated in each group, while in the authors` analysis, the number of females and males was relatively equal. Since sex and smoking have been shown to in uence TLR4 expression, these factors should be treated with caution when designing studies and interpreting results [45][46][47]. Although in the same study, the authors state that elevated expression of TLR4 on monocytes of patients with uncontrolled hypertension indicates their involvement in promoting the in ammatory response, this conclusion may be incorrect.…”

The role of HMGB1/RAGE/TLR4 signaling pathways in cigarette smoke‐induced inflammation in chronic obstructive pulmonary disease

“…Human peripheral blood mononuclear cells obtained from smokers have a higher TLR4 mRNA level than nonsmokers, but this decreases after 2 months of smoking abstinence in COPD patients 107 . This suggests that quitting smoking can reduce TLR4 expression.…”

“…In addition, the smoking index is related to TLR4 IL‐8 and MMP‐9 levels. This may help predict the future risk of developing this disease in smokers without using TLR4 107 . Di Stefano et al 93 detected the expression of some members of the TLR family and inflammatory factors in the airway secretions of patients with severe COPD in a stable stage, accompanied by airway inflammation and bacterial infection.…”

“…106 T A B L E 3 Implication of TLR4 in CS-induced COPD inflammation Human peripheral blood mononuclear cells obtained from smokers have a higher TLR4 mRNA level than nonsmokers, but this decreases after 2 months of smoking abstinence in COPD patients. 107 This suggests that quitting smoking can reduce TLR4 expression. In addition, the smoking index is related to TLR4 IL-8 and MMP-9 levels.…”