Animal Healthcare Flanders, Torhout, Belgium.
Department of Medical and Forensic Pathology, Ghent University, Ghent, Belgium.
PLoS One. 2020 Aug 6;15(8):e0236657. doi: 10.1371/journal.pone.0236657. eCollection 2020.
Crohn's disease is a pathological condition of the gastro-intestinal tract, causing severe transmural inflammation in the ileum and/or colon. Cigarette smoking is one of the best known environmental risk factors for the development of Crohn's disease. Nevertheless, very little is known about the effect of prolonged cigarette smoke exposure on inflammatory modulators in the gut. We examined the effect of cigarette smoke on cytokine profiles in the healthy and inflamed gut of human subjects and in the trinitrobenzene sulphonic acid mouse model, which mimics distal Crohn-like colitis. In addition, the effect of cigarette smoke on epithelial expression of transient receptor potential channels and their concurrent increase with cigarette smoke-augmented cytokine production was investigated. Active smoking was associated with increased IL-8 transcription in ileum of controls (p < 0,001; n = 18-20/group). In the ileum, TRPV1 mRNA levels were decreased in never smoking Crohn's disease patients compared to healthy subjects (p <0,001; n = 20/group). In the colon, TRPV1 mRNA levels were decreased (p = 0,046) in smoking healthy controls (n = 20/group). Likewise, healthy mice chronically exposed to cigarette smoke (n = 10/group) showed elevated ileal Cxcl2 (p = 0,0075) and colonic Kc mRNA levels (p = 0,0186), whereas TRPV1 mRNA and protein levels were elevated in the ileum (p = 0,0315). Although cigarette smoke exposure prior to trinitrobenzene sulphonic acid administration did not alter disease activity, increased pro-inflammatory cytokine production was observed in the distal colon (Kc: p = 0,0273; Cxcl2: p = 0,104; Il1-β: p = 0,0796), in parallel with the increase of Trpv1 mRNA (p < 0,001). We infer that CS affects pro-inflammatory cytokine expression in healthy and inflamed gut, and that the simultaneous modulation of TRPV1 may point to a potential involvement of TRPV1 in cigarette smoke-induced production of inflammatory mediators.
克罗恩病是一种胃肠道的病理状况，会导致回肠和/或结肠出现严重的壁层炎症。吸烟是导致克罗恩病发展的已知的最佳环境风险因素之一。然而，人们对长期吸烟暴露对肠道中炎症调节剂的影响知之甚少。我们研究了香烟烟雾对健康和炎症肠道中细胞因子谱的影响，以及三硝基苯磺酸（TNBS）小鼠模型的影响，该模型模拟了类似远端克罗恩样结肠炎的情况。此外，还研究了香烟烟雾对上皮细胞瞬时受体电位通道表达的影响，以及它们与香烟烟雾增强细胞因子产生的同时增加。在对照组中，主动吸烟与回肠中 IL-8 转录的增加有关（p <0.001；n = 18-20/组）。在回肠中，与健康受试者相比，从未吸烟的克罗恩病患者的 TRPV1 mRNA 水平降低（p <0.001；n = 20/组）。在结肠中，吸烟健康对照组（n = 20/组）的 TRPV1 mRNA 水平降低（p = 0.046）。同样，慢性暴露于香烟烟雾的健康小鼠显示出回肠 Cxcl2（p = 0.0075）和结肠 Kc mRNA 水平升高（p = 0.0186），而 TRPV1 mRNA 和蛋白水平在回肠中升高（p = 0.0315）。尽管在给予三硝基苯磺酸之前暴露于香烟烟雾并没有改变疾病的活动度，但在远端结肠中观察到促炎细胞因子的产生增加（Kc：p = 0.0273；Cxcl2：p = 0.104；Il1-β：p = 0.0796），同时 TRPV1 mRNA 增加（p <0.001）。我们推断 CS 影响健康和炎症肠道中促炎细胞因子的表达，而 TRPV1 的同时调节可能表明 TRPV1 可能参与香烟烟雾诱导的炎症介质产生。
