ArticlePloS one2011
Cigarette smoke extract (CSE) delays NOD2 expression and affects NOD2/RIPK2 interactions in intestinal epithelial cells.
Article in PloS one, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers, 1 of them a synthesis that pooled it.
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Who cites it
14 citing papers in PubMed, 1 synthesis or guideline pooled it, 25 citations in OpenAlex.
- Genetic Factors Interact With Tobacco Smoke to Modify Risk for Inflammatory Bowel Disease in Humans and Mice.Gastroenterology · 2017Pooled it
- RIPK2 promotes colorectal cancer metastasis by protecting YAP degradation from ITCH-mediated ubiquitination.Cell death & disease · 2025Article
- Nicotine in Inflammatory Diseases: Anti-Inflammatory and Pro-Inflammatory Effects.Frontiers in immunology · 2022Review
- Long-Term Follow-Up, Association between CARD15/NOD2 Polymorphisms, and Clinical Disease Behavior in Crohn's Disease Surgical Patients.Mediators of inflammation · 2021Article
- The reduction of DSS-induced colitis severity in mice exposed to cigarette smoke is linked to immune modulation and microbial shifts.Scientific reports · 2020Article
- Nicotine modulates molecules of the innate immune response in epithelial cells and macrophages during infection with M. tuberculosis.Clinical and experimental immunology · 2020Article
- IL-1α and IL-1β promote NOD2-induced immune responses by enhancing MAPK signaling.Laboratory investigation; a journal of technical methods and pathology · 2019Article
- Systematic meta-analyses and field synopsis of genetic and epigenetic studies in paediatric inflammatory bowel disease.Scientific reports · 2016Article
- The microbiota in inflammatory bowel disease.Journal of gastroenterology · 2015Review
- Article
- NOD2 expression is regulated by microRNAs in colonic epithelial HCT116 cells.Inflammatory bowel diseases · 2014Article
- Beyond gene discovery in inflammatory bowel disease: the emerging role of epigenetics.Gastroenterology · 2013Review
- Ursolic acid inhibits cigarette smoke extract-induced human bronchial epithelial cell injury and prevents development of lung cancer.Molecules (Basel, Switzerland) · 2012Article
- A case-only study of gene-environment interaction between genetic susceptibility variants in NOD2 and cigarette smoking in Crohn's disease aetiology.BMC medical genetics · 2012Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundGenetic and environmental factors influence susceptibility to Crohn's disease (CD): NOD2 is the strongest individual genetic determinant and smoking the best-characterised environmental factor. Carriage of NOD2 mutations predispose to small-intestinal, stricturing CD, a phenotype also associated with smoking. We hypothesised that cigarette smoke extract (CSE) altered NOD2 expression and function in intestinal epithelial cells. METHODS AND
findingsIntestinal epithelial cell-lines (SW480, HT29, HCT116) were stimulated with CSE and nicotine (to mimic smoking) ±TNFα (to mimic inflammation). NOD2 expression was measured by qRT-PCR and western blotting; NOD2-RIPK2 interactions by co-immunoprecipitation (CoIP); nuclear NFκB-p65 by ELISA; NFκB activity by luciferase reporter assays and chemokines (CCL20, IL8) in culture supernatants by ELISA. In SW480 and HT29 cells the TNFα-induced NOD2 expression at 4 hours was reduced by CSE (p = 0.0226), a response that was dose-dependent (p = 0.003) and time-dependent (p = 0.0004). Similar effects of CSE on NOD2 expression were seen in cultured ileal biopsies from healthy individuals. In SW480 cells CSE reduced TNFα-induced NFκB-p65 translocation at 15 minutes post-stimulation, upstream of NOD2. Levels of the NOD2-RIPK2 complex were no different at 8 hours post-stimulation with combinations of CSE, nicotine and TNFα, but at 18 hours it was increased in cells stimulated with TNFα+CSE but decreased with TNFα alone (p = 0.0330); CSE reduced TNFα-induced NFκB activity (p = 0.0014) at the same time-point. At 24 hours, basal CCL20 and IL8 (p<0.001 for both) and TNFα-induced CCL20 (p = 0.0330) production were decreased by CSE. CSE also reduced NOD2 expression, CCL20 and IL8 production seen with MDP-stimulation of SW480 cells pre-treated with combinations of TNFα and CSE.
conclusionsCSE delayed TNFα-induced NOD2 mRNA expression and was associated with abnormal NOD2/RIPK2 interaction, reduced NFκB activity and decreased chemokine production. These effects may be involved in the pathogenesis of small-intestinal CD and may have wider implications for the effects of smoking in NOD2-mediated responses.
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