Abstract

Background. Paneth cells are specialized epithelial cells of the small intestine. They contain multiple secretory granules, filled with antimicrobial peptides, which are essential for controlling the growth of microorganisms and maintaining intestinal homeostasis. Alterations in its function are associated with an imbalance of the normal microbiota and inflammatory processes, such as Crohn’s disease (CD). Various studies have shown that cigarette smoke exposure, the main environmental risk factor for CD, affects the intestinal barrier of the small bowel, increasing intestinal bacterial translocation to the underlying lymphoid nodules. However, its effect on Paneth cells is unknown. Objective. To implement a mouse model of intragastric exposition to cigarette smoke condensate (CSC), and to evaluate its impact on Paneth cells (PCs) integrity and functionality. Methods. C57BL/6 male mice (n=4 per group) received 200μg of CSC, 400μg of CSC or vehicle intragastrically, three times a week for two weeks. After two weeks, ileum and colon samples were obtained for histopathological analysis. Also, ileum samples were used to evaluate PCs integrity with Alcian blue/PAS staining protocol, and to quantify the expression of antimicrobial peptides by qPCR. Results. Mice treated with 400ug of CSC exhibited signs of inflammation and distortion ileal, but not colonic, mucosal architecture.; lower number of PCs per crypt (p=0,0017); and reduced expression of cryptdin-1 (p=0,001), cryptdin-4 (p=0,001) and RegIIIγ (p=0,001) compared to the vehicle group. Mice treated with the lower dose of CSC only showed a reduced expression of RegIIIγ compared to the vehicle group. The distribution of PCs granules was not significantly different between the three groups. Conclusion. It was possible to implement a model of intragastric exposure to cigarette smoke in mice, which induces ileal inflammation. Moreover, our results show that the exposure to cigarette compounds alters Paneth cells integrity and functionality. This effect may promote gastrointestinal infections, or trigger inflammatory processes.