Background: Inflammatory bowel disease (IBD) is a chronic inflammatory disease affecting the gastrointestinal tract, which consists of two major forms: Crohn's disease (CD) and Ulcerative Colitis (UC). The impact of cigarette smoking on IBD has been well established by a large number of epidemiological studies in which exposure to cigarette smoke was associated with a higher risk of developing CD and with an increased severity in CD patients. By contrast, cigarette smoking was shown to be protective against UC. The incidence of UC is 2.5 times less frequent in smokers, and, after disease onset, it has been reported that smoking improves the course of the disease, decreases the frequency of flare-up episodes, decreases the need for steroid administration, and decreases the colectomy rate. It has also been established that smoking cessation improves CD and worsens UC. While there are numerous descriptive and epidemiological publications about cigarette smoking and IBD, few mechanistic studies have explored the effect of cigarette smoke exposure on intestinal inflammation.
Methods: This study evaluated the impact of mainstream cigarette smoke (CS) on the severity of dextran sulfate sodium (DSS)-induced UC in C57BL/6 female mice. UC-like symptoms were induced using DSS administered through drinking water at a concentration of 5.0%. Three groups of animals, low, medium, and high exposure groups, were exposed to CS to a target concentration of 750 μg/l total particulate matter for 1, 2, and 4 h per day, respectively. A 2-week CS pre-exposure period (including a 6-day concentration adaptation to the target CS concentration) was included to acclimatize the animals to the target CS concentration. This was followed by an 8-day CS treatment combined with DSS or control (drinking water only), after which the animals were evaluated for the progression and severity of UC symptoms.
Results: Using a comprehensive profiling approach (transcriptomics and proteomics) together with classical endpoint analysis (body weight, cytokine release assays), we were able to show a protective CS-related effect on the development of UC. Interestingly, although a reduction in the inflammatory state of CS-exposed mice was observed, different molecular processes were activated depending on CS exposure timing and colon localization.
Conclusions: The current study enables the investigation of possible molecular mechanisms responsible for the attenuation of UC by CS exposure.