Abstract
IL-1 is a pleiotropic cytokine that controls inflammation, immunity, and hemopoiesis. The major IL-1 agonistic molecules are IL-1α and IL-1β, which bind to IL-1R type I (IL-1R1) and induce similar biologic functions. The IL-1R antagonist (IL-1Ra) is a physiologic inhibitor of IL-1R1 signaling. In the tumor microenvironment, IL-1 is expressed by malignant, stromal, and infiltrating cells and supports tumor invasiveness and progression. We have shown that in the tumor microenvironment, the IL-1 agonistic molecules act different as a result of their local amounts and their compartmentalization within the producing cells. IL-1β is produced mainly by myeloid cells upon inflammatory stimulation and is active as a mature, secreted molecule. The precursor of IL-1α (ProIL-1α) is biologically active; it is constitutively expressed in diverse tissue cells in basal levels, and its expression increases during stress or inflammation. ProIL-1α is mainly located in the cytosol or it is membrane associated. ProIL-1α also translocates into the nucleus and binds to chromatin. ProIL-1α is rarely actively secreted but is released from necrotizing tissues and serves as "alarmin" for initiation of inflammation. In the tumor microenvironment, IL-1β pr...Continue Reading
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