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Interleukin-1 Beta-A Friend or Foe in Malignancies?


ABSTRACT: Interleukin-1 beta (IL-1?) is induced by inflammatory signals in a broad number of immune cell types. IL-1? (and IL-18) are the only cytokines which are processed by caspase-1 after inflammasome-mediated activation. This review aims to summarize current knowledge about parameters of regulation of IL-1? expression and its multi-facetted role in pathophysiological conditions. IL-1 signaling activates innate immune cells including antigen presenting cells, and drives polarization of CD4+ T cells towards T helper type (Th) 1 and Th17 cells. Therefore, IL-1? has been attributed a largely beneficial role in resolving acute inflammations, and by initiating adaptive anti-tumor responses. However, IL-1? generated in the course of chronic inflammation supports tumor development. Furthermore, IL-1? generated within the tumor microenvironment predominantly by tumor-infiltrating macrophages promotes tumor growth and metastasis via different mechanisms. These include the expression of IL-1 targets which promote neoangiogenesis and of soluble mediators in cancer-associated fibroblasts that evoke antiapoptotic signaling in tumor cells. Moreover, IL-1 promotes the propagation of myeloid-derived suppressor cells. Using genetic mouse models as well as agents for pharmacological inhibition of IL-1 signaling therapeutically applied for treatment of IL-1 associated autoimmune diseases indicate that IL-1? is a driver of tumor induction and development.

SUBMITTER: Bent R 

PROVIDER: S-EPMC6121377 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature

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Interleukin-1 Beta-A Friend or Foe in Malignancies?

Bent Rebekka R   Moll Lorna L   Grabbe Stephan S   Bros Matthias M  

International journal of molecular sciences 20180724 8


Interleukin-1 beta (IL-1β) is induced by inflammatory signals in a broad number of immune cell types. IL-1β (and IL-18) are the only cytokines which are processed by caspase-1 after inflammasome-mediated activation. This review aims to summarize current knowledge about parameters of regulation of IL-1β expression and its multi-facetted role in pathophysiological conditions. IL-1 signaling activates innate immune cells including antigen presenting cells, and drives polarization of CD4+ T cells to  ...[more]

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