Aim
Ulcerative colitis (UC) is an autoimmune disease characterized by inflammation in the gastrointestinal tract. The severity of UC is higher in nonsmokers than smokers; however, the biological mechanisms controlling this effect remain unknown. The aim of this study was to examine the effect of cigarette smoke extract (CSE) on inflamed and noninflamed colonic tissue from UC patients and to determine if inflammatory mediators, transcription factors, and T cell phenotypes are altered by CSE.
Conclusion
These data suggest that observed effects of CSE in reducing inflammatory mediators ex vivo are specific to inflamed colonic tissue but are not due to the activation of NF-κB or HIF-1α and are not caused by alterations in subpopulations of T cells in these UC tissues.
Methods
Blood and colonic biopsies were obtained from UC patients undergoing endoscopy. Biopsies were cultured in the presence or absence of CSE. Multiplex enzyme-linked immunosorbent assay (ELISA) measured secreted levels of inflammatory mediators. Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and Hypoxia-inducible factor 1-alpha (HIF-1α) expression were measured by DNA-binding ELISA. T cell phenotypes were assessed by flow cytometry in matched blood and biopsies.
Results
Secreted levels of interleukin 2 (IL-2), interleukin 6 (IL-6), tumor necrosis factor - alpha (TNF-α), chemokine (C-C motif) ligand 2 (CCL2), and interleukin 10 (IL-10) were significantly (all P < 0.05) decreased following treatment with CSE. This effect was specific to inflamed tissue and was not observed in noninflamed tissue. CSE did not alter the expression of NF-κB or HIF-1α. Assessment of T cell phenotypes in blood and tissue revealed that there were significantly more activated and exhausted T cells in the colonic tissue compared to matched blood. These profiles were not altered following CSE treatment.