PMC:3342329 / 21382-23408 JSONTXT

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It has been reported that IL-1 induces the activation of NF-κB in several cancers, and increases cell cycle progression, and the suppression of apoptotic cell death leading to tumor promotion. The results of various studies over the past 10 years indicate that the major function of IL-1Ra is to regulate the pleiotropic effects of IL-1 by competitively blocking its functions [47]. The ability of IL-1 to induce its own antagonist is of interest in understanding the regulation and dysregulation of IL-1 signaling in normal and diseased tissue. Up-regulation of the receptor antagonist represents a mechanism for turning off IL-1 signaling and creating a temporary state of refractoriness. The elevated expression of IL-1Ra, without any change of IL-1 in tumors, suggests that the IL-1-signaling system may be dysregulated by IL-1Ra in tumors. IL-1Ra has been shown to inhibit tumor progression in prostate, breast, and skin cancer [14], [15], [16]. Intracellular IL-1Ra (icIL-1Ra) inhibits IL-6 and IL-8 production in Caco-2 cells by blocking NF-κB pathways [37]. We found that the levels of IL-1Ra were significantly elevated in the tumor tissues of CCR5−/− mice inoculated with B16 melanoma cells. Taken together, these data indicate IL-1Ra could be critically involved in the tumor growth inhibition of CCR5−/− mice through the inactivation of NF-κB in the present 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