Abstract
Interleukin-1 (IL-1) is a major “alarm” upstream pro-inflammatory cytokine that mainly acts by inducing cascades of cytokine and inflammation-promoting mediators. In the tumor arena, IL-1 is produced by both malignant and microenvironmental cells. IL-1α and IL-1β are the major agonists of IL-1, while IL-1Ra is a physiological inhibitor of pre-formed IL-1. IL-1α and IL-1β differ in their compartmentalization and in the producing cells. IL-1β is only active in its inflammasome dependent processed and secreted form and has been considered as the major mediator of inflammation. On the other hand, IL-1α is mainly cell-associated in tissue resident cells, being also active in its precursor form. The role of the IL-1 molecules in the unique microenvironment in the colon is largely unknown. Here, we described the role of IL-1α and IL-1β in colon homeostasis, colon inflammation, colon carcinogenesis and invasiveness of colorectal cancer. Understanding of the integrative role of IL-1α and IL-1β in these processes will facilitate the application of novel IL-1 modulating approaches.
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Acknowledgments
Ron N. Apte and Elena Voronov have been supported by the Israel Ministry of Science (MOS) jointly with the Deutsches Krebsforschungscentrum (DKFZ), Heidelberg, Germany, the Israel Science Foundation funded by the Israel Academy of Sciences and Humanities, the Israel Cancer Association and the Israel Ministry of Health Chief Scientist’s Office, FP7: “Cancer and Inflammation” (INFLA-CARE), The Binational (Israel-USA) Science Foundation (BSF) and the German-Israeli Foundation (GIF). Prof. Ron N. Apte is an incumbent of the Irving Isaac Sklar Chair in Endocrinology and Cancer.
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Voronov, E., Apte, R.N. IL-1 in Colon Inflammation, Colon Carcinogenesis and Invasiveness of Colon Cancer. Cancer Microenvironment 8, 187–200 (2015). https://doi.org/10.1007/s12307-015-0177-7
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DOI: https://doi.org/10.1007/s12307-015-0177-7