Nutlin-3a Inhibits the Production of CXCL10 by Ionizing Radiation in J774A.1 Murine Macrophages

초록

Nutlin-3a inhibits the interaction between p53, a tumor suppressor protein, and MDM2, an E3 ubiquitin ligase, thereby stabilizing and activating p53. Although the pathophysiological effects of Nutlin-3a, based on its activation of p53, have been documented, studies on its impacts on radiation-exposed macrophages remain sparse. This study explored the modulatory effect of Nutlin-3a on ionizing radiation (IR)-induced CXCL10 production in J774A.1 murine macrophages. Nutlin-3a reduces IR-induced CXCL10 production in these cells and also inhibits IR-induced p38 MAPK activation in the same macrophages. Moreover, using pifithrin-α, a pharmacological inhibitor of p53, it was demonstrated that the inhibitory effect of Nutlin-3a on IRinduced CXCL10 in J774A.1 macrophages is independent of p53. To the best of our knowledge, this study is the first to report the pathophysiological significance that the regulation of p38 MAPK phosphorylation by Nutlin-3a controls IR-induced CXCL10 production in J774A.1 macrophages.

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