Abstract Background Smoking exerts opposite effects on inflammatory bowel diseases (IBD): it worsens Crohn’s disease (CD) while appearing protective in ulcerative colitis (UC).1 The specific tobacco component responsible for these contrasting effects remains unclear. Adipose-derived mesenchymal stem cells (AdMSCs) from the mesentery play a key role in immune regulation and intestinal homeostasis. Our group previously reported functional impairments in these cells in CD, potentially contributing to local inflammation.2,3 Here, we explored whether nicotine, a key bioactive compound of tobacco, contributes to these alterations and whether its effects differ between CD and UC. Methods Adipose tissue biopsies were obtained AdMSCs from non-smoking CD patients (n = 6). AdMSCs were isolated and characterized by flow cytometry using a panel of positive and negative membrane surface markers (CD90+, CD105+, CD45, CD34-). All the experiments were performed in passage 3. AdMSCs were exposed to nicotine (0, 1, 5, and 10 µM) for 24h. Expression of pro- and anti-inflammatory cytokines (IL1B, IL6, CCL2, IL10) were quantified by qPCR and ELISA, and apoptotic balance (BAX/BCL2 ratio) was assessed. In a complementary ex vivo approach, mesenteric explants from non-smoking CD and UC patients (n = 3 per group) were incubated with nicotine (0, 1, and 10 µM) to evaluate inflammatory (IL6, IL1B and TNF), oxidative stress (HSPA5), anti-inflammatory (IL 10 and IL13), and immune (NOD2) markers. Results In CD-derived AdMSCs, nicotine at 1 µM, significantly upregulated CCL2, IL6, and IL1B expression, without affecting the BAX/BCL2 ratio. Higher concentrations did not further modify this response, suggesting a maximal effect at low doses.Ex vivo, nicotine induced opposite responses in CD and UC mesenteric explants: in CD, it increased pro-inflammatory and oxidative stress markers, whereas in UC, these parameters tended to decrease. Conclusion Nicotine promotes a pro-inflammatory phenotype in mesenteric AdMSCs and adipose tissue from CD patients, while its impact in UC appears blunted. These opposing cellular effects may mechanistically underlie the divergent clinical influence of smoking in IBD, highlighting the mesenteric adipose compartment as a key mediator of tobacco-driven immune modulation. References: 1 Berkowitz L et al. Front. Immunol, 2018. 9:74 2 Boronat-Toscano A et al. Cells, 2023. 27;12(7):1021 3 Serena C et al. Stem Cell Reports, 2017. 10;9(4):1109-1123 Conflict of interest: Dr. Ginés Mir, Iris: No conflict of interest Monfort-Ferré, Diandra: No conflict of interest Boronat-Toscano, Albert: No conflict of interest Ramirez, Noelia: No conflict of interest Caro, Aleidis: No conflict of interest Menacho, Margarita: No conflicts Clua, Laura: No conflict of interest Cepero, Claudia: No conflict of interest Valldossera, Gemma: No conflict of interest Mañas, M. José: No conflict of interest Suau, Roger: I declare that no conflicts of interest exist related to the authors’ work, study, or project, and that have no financial or personal relationships that could compromise objectivity. Manyé Almero, Josep: No conflict of interest Serena, Carolina: None conflict of interest
Mir et al. (Thu,) studied this question.