Tobacco Alkaloid Assessment in a DSS-Induced Colitis Mouse Model with a Fully Humanized Immune System
Inflammatory bowel disease (IBD) refers to chronic intestinal immune-mediated diseases including two main disease manifestations: ulcerative colitis (UC) and Crohn’s disease (CD). Epidemiological, clinical, and preclinical evidence has highlighted the potential anti-inflammatory properties of natura...
| Main Authors: | , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2023-03-01
|
| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/24/7/6419 |
| _version_ | 1797607825907646464 |
|---|---|
| author | Catherine Verhaeghe Marja Talikka Alain Sewer Nicolas Sierro Mehdi Auberson Dariusz Peric David Bornand Remi Dulize Emmanuel Guedj Patrick Nef Sebastien P. Tabruyn Julia Hoeng Manuel C. Peitsch Giuseppe Lo Sasso |
| author_facet | Catherine Verhaeghe Marja Talikka Alain Sewer Nicolas Sierro Mehdi Auberson Dariusz Peric David Bornand Remi Dulize Emmanuel Guedj Patrick Nef Sebastien P. Tabruyn Julia Hoeng Manuel C. Peitsch Giuseppe Lo Sasso |
| author_sort | Catherine Verhaeghe |
| collection | DOAJ |
| description | Inflammatory bowel disease (IBD) refers to chronic intestinal immune-mediated diseases including two main disease manifestations: ulcerative colitis (UC) and Crohn’s disease (CD). Epidemiological, clinical, and preclinical evidence has highlighted the potential anti-inflammatory properties of naturally occurring alkaloids. In the present study, we investigated the potential anti-inflammatory activities of the tobacco alkaloids nicotine and anatabine in a dextran sulfate sodium (DSS)-induced UC mouse model with a fully humanized immune system. Our results show that nicotine significantly reduced all acute colitis symptoms and improved colitis-specific endpoints, including histopathologically assessed colon inflammation, tissue damage, and mononuclear cell infiltration. The tobacco alkaloid anatabine showed similar effectiveness trends, although they were generally weaker or not significant. Gene expression analysis in the context of biological network models of IBD further pinpointed a possible mechanism by which nicotine attenuated DSS-induced colitis in humanized mice. The current study enables further investigation of possible molecular mechanisms by which tobacco alkaloids attenuate UC symptoms. |
| first_indexed | 2024-03-11T05:35:08Z |
| format | Article |
| id | doaj.art-ad32ff372e02472dab8203d1027b10af |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-11T05:35:08Z |
| publishDate | 2023-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-ad32ff372e02472dab8203d1027b10af2023-11-17T16:50:56ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-03-01247641910.3390/ijms24076419Tobacco Alkaloid Assessment in a DSS-Induced Colitis Mouse Model with a Fully Humanized Immune SystemCatherine Verhaeghe0Marja Talikka1Alain Sewer2Nicolas Sierro3Mehdi Auberson4Dariusz Peric5David Bornand6Remi Dulize7Emmanuel Guedj8Patrick Nef9Sebastien P. Tabruyn10Julia Hoeng11Manuel C. Peitsch12Giuseppe Lo Sasso13TransCure bioServices, Av Marie Curie 260, FR-74160 Archamps, FrancePMI R&D, Philip Morris Products S.A., Quai Jeanrenaud 5, CH-2000 Neuchâtel, SwitzerlandPMI R&D, Philip Morris Products S.A., Quai Jeanrenaud 5, CH-2000 Neuchâtel, SwitzerlandPMI R&D, Philip Morris Products S.A., Quai Jeanrenaud 5, CH-2000 Neuchâtel, SwitzerlandPMI R&D, Philip Morris Products S.A., Quai Jeanrenaud 5, CH-2000 Neuchâtel, SwitzerlandPMI R&D, Philip Morris Products S.A., Quai Jeanrenaud 5, CH-2000 Neuchâtel, SwitzerlandPMI R&D, Philip Morris Products S.A., Quai Jeanrenaud 5, CH-2000 Neuchâtel, SwitzerlandPMI R&D, Philip Morris Products S.A., Quai Jeanrenaud 5, CH-2000 Neuchâtel, SwitzerlandPMI R&D, Philip Morris Products S.A., Quai Jeanrenaud 5, CH-2000 Neuchâtel, SwitzerlandTransCure bioServices, Av Marie Curie 260, FR-74160 Archamps, FranceTransCure bioServices, Av Marie Curie 260, FR-74160 Archamps, FrancePMI R&D, Philip Morris Products S.A., Quai Jeanrenaud 5, CH-2000 Neuchâtel, SwitzerlandPMI R&D, Philip Morris Products S.A., Quai Jeanrenaud 5, CH-2000 Neuchâtel, SwitzerlandPMI R&D, Philip Morris Products S.A., Quai Jeanrenaud 5, CH-2000 Neuchâtel, SwitzerlandInflammatory bowel disease (IBD) refers to chronic intestinal immune-mediated diseases including two main disease manifestations: ulcerative colitis (UC) and Crohn’s disease (CD). Epidemiological, clinical, and preclinical evidence has highlighted the potential anti-inflammatory properties of naturally occurring alkaloids. In the present study, we investigated the potential anti-inflammatory activities of the tobacco alkaloids nicotine and anatabine in a dextran sulfate sodium (DSS)-induced UC mouse model with a fully humanized immune system. Our results show that nicotine significantly reduced all acute colitis symptoms and improved colitis-specific endpoints, including histopathologically assessed colon inflammation, tissue damage, and mononuclear cell infiltration. The tobacco alkaloid anatabine showed similar effectiveness trends, although they were generally weaker or not significant. Gene expression analysis in the context of biological network models of IBD further pinpointed a possible mechanism by which nicotine attenuated DSS-induced colitis in humanized mice. The current study enables further investigation of possible molecular mechanisms by which tobacco alkaloids attenuate UC symptoms.https://www.mdpi.com/1422-0067/24/7/6419ulcerative colitisalkaloidsmouse modelnicotine |
| spellingShingle | Catherine Verhaeghe Marja Talikka Alain Sewer Nicolas Sierro Mehdi Auberson Dariusz Peric David Bornand Remi Dulize Emmanuel Guedj Patrick Nef Sebastien P. Tabruyn Julia Hoeng Manuel C. Peitsch Giuseppe Lo Sasso Tobacco Alkaloid Assessment in a DSS-Induced Colitis Mouse Model with a Fully Humanized Immune System International Journal of Molecular Sciences ulcerative colitis alkaloids mouse model nicotine |
| title | Tobacco Alkaloid Assessment in a DSS-Induced Colitis Mouse Model with a Fully Humanized Immune System |
| title_full | Tobacco Alkaloid Assessment in a DSS-Induced Colitis Mouse Model with a Fully Humanized Immune System |
| title_fullStr | Tobacco Alkaloid Assessment in a DSS-Induced Colitis Mouse Model with a Fully Humanized Immune System |
| title_full_unstemmed | Tobacco Alkaloid Assessment in a DSS-Induced Colitis Mouse Model with a Fully Humanized Immune System |
| title_short | Tobacco Alkaloid Assessment in a DSS-Induced Colitis Mouse Model with a Fully Humanized Immune System |
| title_sort | tobacco alkaloid assessment in a dss induced colitis mouse model with a fully humanized immune system |
| topic | ulcerative colitis alkaloids mouse model nicotine |
| url | https://www.mdpi.com/1422-0067/24/7/6419 |
| work_keys_str_mv | AT catherineverhaeghe tobaccoalkaloidassessmentinadssinducedcolitismousemodelwithafullyhumanizedimmunesystem AT marjatalikka tobaccoalkaloidassessmentinadssinducedcolitismousemodelwithafullyhumanizedimmunesystem AT alainsewer tobaccoalkaloidassessmentinadssinducedcolitismousemodelwithafullyhumanizedimmunesystem AT nicolassierro tobaccoalkaloidassessmentinadssinducedcolitismousemodelwithafullyhumanizedimmunesystem AT mehdiauberson tobaccoalkaloidassessmentinadssinducedcolitismousemodelwithafullyhumanizedimmunesystem AT dariuszperic tobaccoalkaloidassessmentinadssinducedcolitismousemodelwithafullyhumanizedimmunesystem AT davidbornand tobaccoalkaloidassessmentinadssinducedcolitismousemodelwithafullyhumanizedimmunesystem AT remidulize tobaccoalkaloidassessmentinadssinducedcolitismousemodelwithafullyhumanizedimmunesystem AT emmanuelguedj tobaccoalkaloidassessmentinadssinducedcolitismousemodelwithafullyhumanizedimmunesystem AT patricknef tobaccoalkaloidassessmentinadssinducedcolitismousemodelwithafullyhumanizedimmunesystem AT sebastienptabruyn tobaccoalkaloidassessmentinadssinducedcolitismousemodelwithafullyhumanizedimmunesystem AT juliahoeng tobaccoalkaloidassessmentinadssinducedcolitismousemodelwithafullyhumanizedimmunesystem AT manuelcpeitsch tobaccoalkaloidassessmentinadssinducedcolitismousemodelwithafullyhumanizedimmunesystem AT giuseppelosasso tobaccoalkaloidassessmentinadssinducedcolitismousemodelwithafullyhumanizedimmunesystem |