Impact of Smoking Cigarette on the mRNA Expression of Cytokines in Mucosa of Inflammatory Bowel Disease

Abstract

It is well known that smoking is the risk factor in the development and clinical course of Crohn´'s disease (CD), but on the other hand, smoking is a protective factor against ulcerative colitis (UC). The pathways that are influenced by smoking in CD and UC are poorly understood. The aim of our study was to analyse the influence of smoking on the mRNA expression of cytokines in mucosa in patients with CD and UC. We performed a cross-sectional study. The cohort consisted of 86 IBD patients (48 CD patients and 38 UC patients) and took place at the IBD Centre at the University Hospital Bratislava-Ružinov. We took the demographic and clinical data of each patient, including information about their smoking habits. We performed a colonoscopy on each patient and took biopsies from both inflamed and non-inflamed sigma (CD, UC) and terminal ileum (CD). mRNA was extracted from mucosal biopsy samples for each cytokine and was normalized to a housekeeping gene (GAPDH). Finally, we compared the mRNA expression of target cytokines in the mucosa of smokers and non-smokers in IBD patients. Smokers with Crohn's disease have a significantly higher mRNA expression of pro-inflammatory cytokine TNF α (p=0.003) in inflamed mucosa in sigma compared with non-smokers. In smokers with ulcerative colitis, we observed significantly higher mRNA expression of anti-inflammatory cytokine IL 10 (p=0.022) in non-inflamed mucosa of sigma. Similarly, smokers with UC have a significantly decreased mRNA expression of cytokine TLR 2 (p=0.024) and CCR1(p=0.049) in non-inflamed mucosa of sigma. Based on our results, smoking has a positive influence on cessation and the clinical course of UC due to the stimulation of anti-inflammatory cytokine IL 10 in mucosa. On the other hand, smokers with CD have a higher expression of pro-inflammatory cytokine TNF α, which could be associated with a worsening of the disease and response to therapy.

Impact of Cigarette Smoking on the Risk of Osteoporosis in Inflammatory Bowel Diseases

“…Among the UC patients, nicotine's potentially beneficial impact has been associated with the activation of α7-nAChR in immune cells, e.g., in the macrophages and dendritic cells. A stimulation of these receptors decreases TNF-α and IL-2, which are the pro-inflammatory cytokines, and inhibits the function of CD4+ and CD25+ regulating T lymphocytes [124].…”

Review article: impact of cigarette smoking on intestinal inflammation—direct and indirect mechanisms

“…52 In a recent cross-sectional study, the mRNA levels of various cytokines were measured in mucosa biopsies from inflamed and no-inflamed areas in inflammatory bowel disease patients. 215 They found that smokers with Crohn's disease TA B L E 2 Genetic risk alleles and smoking correlation in inflammatory bowel disease…”

“…Also, in smokers with ulcerative colitis, they observed significantly higher IL10 mRNA levels in non-inflamed mucosa. 215 Another study, on expression on colonic detoxification genes, showed that of the 244 detoxification genes investigated, 65 were dysregulated in ulcerative colitis patients in comparison to healthy controls or Crohn's disease patients. 216 Of the 65 genes dysregulated, 43…”

“…Quantitative real‐time polymerase chain reaction performed on inflamed vs non‐inflamed biopsies from ileal Crohn's disease patients showed that active smokers had downregulated angiotensinogen mRNA levels 52 . In a recent cross‐sectional study, the mRNA levels of various cytokines were measured in mucosa biopsies from inflamed and no‐inflamed areas in inflammatory bowel disease patients 215 . They found that smokers with Crohn's disease had significantly higher TNF mRNA levels in inflamed mucosa compared with nonsmokers.…”