PMID- 33319055 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20220419 IS - 2397-9070 (Electronic) IS - 2397-9070 (Linking) VI - 4 IP - 6 DP - 2020 Dec TI - Effect of cigarette smoke extract on the intestinal microenvironment of ulcerative colitis tissue. PG - 1191-1198 LID - 10.1002/jgh3.12422 [doi] AB - BACKGROUND AND 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. 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-kappaB) and Hypoxia-inducible factor 1-alpha (HIF-1alpha) 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-alpha), 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-kappaB or HIF-1alpha. 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. 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-kappaB or HIF-1alpha and are not caused by alterations in subpopulations of T cells in these UC tissues. CI - (c) 2020 The Authors. JGH Open: An open access journal of gastroenterology and hepatology published by Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd. FAU - Cannon, Aoife AU - Cannon A AUID- ORCID: 0000-0002-7739-5528 AD - Department of Surgery Trinity Translational Medicine Institute, Trinity College Dublin Dublin Ireland. FAU - Clarke, Niamh AU - Clarke N AD - Department of Surgery Trinity Translational Medicine Institute, Trinity College Dublin Dublin Ireland. FAU - MacCarthy, Finbar AU - MacCarthy F AD - Department of Clinical Medicine Trinity Translational Medicine Institute, St. James's Hospital Dublin Ireland. AD - Department of Gastroenterology SACC Directorate, St. James's Hospital Dublin Ireland. FAU - Dunne, Cara AU - Dunne C AD - Department of Clinical Medicine Trinity Translational Medicine Institute, St. James's Hospital Dublin Ireland. AD - Department of Gastroenterology SACC Directorate, St. James's Hospital Dublin Ireland. FAU - Kevans, David AU - Kevans D AD - Department of Clinical Medicine Trinity Translational Medicine Institute, St. James's Hospital Dublin Ireland. AD - Department of Gastroenterology SACC Directorate, St. James's Hospital Dublin Ireland. FAU - Mahmud, Nasir AU - Mahmud N AD - Department of Clinical Medicine Trinity Translational Medicine Institute, St. James's Hospital Dublin Ireland. AD - Department of Gastroenterology SACC Directorate, St. James's Hospital Dublin Ireland. FAU - Lysaght, Joanne AU - Lysaght J AD - Department of Surgery Trinity Translational Medicine Institute, Trinity College Dublin Dublin Ireland. FAU - O'Sullivan, Jacintha AU - O'Sullivan J AD - Department of Surgery Trinity Translational Medicine Institute, Trinity College Dublin Dublin Ireland. LA - eng PT - Journal Article DEP - 20201021 PL - Australia TA - JGH Open JT - JGH open : an open access journal of gastroenterology and hepatology JID - 101730833 PMC - PMC7731828 OTO - NOTNLM OT - T lymphocytes OT - cigarette smoke extract OT - inflammatory bowel disease OT - inflammatory proteins OT - smoking EDAT- 2020/12/16 06:00 MHDA- 2020/12/16 06:01 PMCR- 2020/10/21 CRDT- 2020/12/15 06:05 PHST- 2019/10/17 00:00 [received] PHST- 2020/03/21 00:00 [revised] PHST- 2020/09/20 00:00 [accepted] PHST- 2020/12/15 06:05 [entrez] PHST- 2020/12/16 06:00 [pubmed] PHST- 2020/12/16 06:01 [medline] PHST- 2020/10/21 00:00 [pmc-release] AID - JGH312422 [pii] AID - 10.1002/jgh3.12422 [doi] PST - epublish SO - JGH Open. 2020 Oct 21;4(6):1191-1198. doi: 10.1002/jgh3.12422. eCollection 2020 Dec.