Ornithine Decarboxylase in Macrophages Exacerbates Colitis and Promotes Colitis-Associated Colon Carcinogenesis by Impairing M1 Immune Responses

Cancer Research
Kshipra SinghKeith T Wilson

Abstract

Ornithine decarboxylase (ODC) is the rate-limiting enzyme for polyamine biosynthesis and restricts M1 macrophage activation in gastrointestinal (GI) infections. However, the role of macrophage ODC in colonic epithelial-driven inflammation is unknown. Here, we investigate cell-specific effects of ODC in colitis and colitis-associated carcinogenesis (CAC). Human colonic macrophages expressed increased ODC levels in active ulcerative colitis and Crohn's disease, colitis-associated dysplasia, and CAC. Mice lacking Odc in myeloid cells (OdcΔmye mice) that were treated with dextran sulfate sodium (DSS) exhibited improved survival, body weight, and colon length and reduced histologic injury versus control mice. In contrast, GI epithelial-specific Odc knockout had no effect on clinical parameters. Despite reduced histologic damage, colitis tissues of OdcΔmye mice had increased levels of multiple proinflammatory cytokines and chemokines and enhanced expression of M1, but not M2 markers. In the azoxymethane-DSS model of CAC, OdcΔmye mice had reduced tumor number, burden, and high-grade dysplasia. Tumors from OdcΔmye mice had increased M1, but not M2 macrophages. Increased levels of histone 3, lysine 9 acetylation, a marker of open chroma...Continue Reading

References

Nov 1, 1990·The New England Journal of Medicine·A EkbomH O Adami
Apr 24, 2002·The Journal of Immunology : Official Journal of the American Association of Immunologists·Alain P GobertKeith T Wilson
Dec 7, 2005·International Journal of Cancer. Journal International Du Cancer·Emi OsawaTaeko Dohi
Feb 7, 2006·The Journal of Biological Chemistry·Anthony E Pegg
Aug 5, 2006·Journal of Leukocyte Biology·Joseph E QuallsDonald A Cohen
Oct 26, 2006·Nature Reviews. Immunology·Gavin P DunnRobert D Schreiber
May 15, 2007·Lancet·Daniel C Baumgart, Simon R Carding
May 1, 2009·Nature Reviews. Gastroenterology & Hepatology·Linda A FeaginsStuart J Spechler
Feb 16, 2010·IUBMB Life·Marina S DrutskayaSergei A Nedospasov
Apr 28, 2010·Gastroenterology·Janos TerzićMichael Karin
Jul 14, 2010·The Journal of Experimental Medicine·Rosalba SalcedoGiorgio Trinchieri
Feb 10, 2011·Cancer Research·Caitlyn W BarrettChristopher S Williams
Jun 12, 2012·Journal of Leukocyte Biology·Sergey V NovitskiyHarold L Moses
Jul 4, 2012·International Journal of Cancer. Journal International Du Cancer·Geethanjali PickertIrmgard Tegeder
Oct 31, 2012·International Journal of Molecular Sciences·Giovanni MonteleoneCarmine Stolfi
May 25, 2013·American Journal of Physiology. Gastrointestinal and Liver Physiology·Kshipra SinghKeith T Wilson
Aug 12, 2014·The Journal of Immunology : Official Journal of the American Association of Immunologists·Alain P GobertKeith T Wilson
Sep 18, 2014·Frontiers in Immunology·Silvia Galván-Peña, Luke A J O'Neill
Feb 5, 2015·Nature Reviews. Molecular Cell Biology·Swaminathan Venkatesh, Jerry L Workman
Apr 9, 2015·The New England Journal of Medicine·Laurent Beaugerie, Steven H Itzkowitz
Dec 15, 2015·The Journal of Immunology : Official Journal of the American Association of Immunologists·Cong YeBin Zhang
May 28, 2016·American Journal of Physiology. Gastrointestinal and Liver Physiology·Raymond A Isidro, Caroline B Appleyard
Jun 9, 2016·The Journal of Biological Chemistry·Anthony E Pegg
Jun 22, 2016·Advances in Experimental Medicine and Biology·Luca CassettaJeffrey W Pollard
Aug 3, 2016·The Journal of Clinical Investigation·Dana M HardbowerKeith T Wilson
Jan 18, 2017·Proceedings of the National Academy of Sciences of the United States of America·Dana M HardbowerKeith T Wilson
Jan 28, 2017·Future Oncology·George A AlexiouAthanassios P Kyritsis
Oct 14, 2017·American Journal of Physiology. Gastrointestinal and Liver Physiology·Jackie E BaderE Angela Murphy

❮ Previous
Next ❯

Citations

Sep 6, 2018·Nature Reviews. Cancer·Robert A CaseroAnthony E Pegg
Apr 25, 2019·Amino Acids·Yvonne L LatourKeith T Wilson
Apr 12, 2019·Frontiers in Cellular and Infection Microbiology·Kshipra SinghKeith T Wilson
Feb 20, 2020·Amino Acids·Enzo Agostinelli
Jun 9, 2020·Frontiers in Cell and Developmental Biology·Mehdi ChaibLiza Makowski
Oct 28, 2019·Molecular Therapy Oncolytics·Xiaoming ZhongZhiwen Yang
Nov 16, 2020·Gastroenterology·Alain P GobertKeith T Wilson
Jan 10, 2021·Cancers·Yang ZhangJing Wang
Feb 6, 2021·Digestive and Liver Disease : Official Journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver·Massimo Claudio Fantini, Ilaria Guadagni
Jan 14, 2020·Biochemical Pharmacology·Tao YuJae Youl Cho
May 1, 2021·International Journal of Molecular Sciences·Qiang PengChi-Fai Ng
Sep 17, 2021·Journal of the American Medical Informatics Association : JAMIA·Lawrence BaiPurvesh Khatri
Nov 13, 2021·Gastroenterology·Alain P GobertKeith T Wilson

❮ Previous
Next ❯

Related Concepts

Related Feeds

Cancer Epigenetics Chromatin Complexes (Keystone)

Epigenetic changes are present and dysregulated in many cancers, including DNA methylation, non-coding RNA segments and post-translational protein modifications. The epigenetic changes may or may not provide advantages for the cancer cells. This feed focuses on chromatin complexes and their role in cancer epigenetics.

Cancer Epigenetics and Chromatin (Keystone)

Epigenetic changes are present and dysregulated in many cancers, including DNA methylation, non-coding RNA segments and post-translational protein modifications. The epigenetic changes may or may not provide advantages for the cancer cells. This feed focuses on chromatin and its role in cancer epigenetics please follow this feed to learn more.