Subcellular localization of key proteins regulates inflammatory response

Recently, researchers from Osaka University revealed the effect of subcellular localization of arid5a on inflammatory response Previously, we have known that the protein into the nucleus will promote the immune response, but located in the cytoplasm will block the inflammatory response   Tadamitsu Kishimoto, a professor from the center for immunology of Osaka University, and others found that the subcellular localization of arid5a can regulate the inflammatory response In this study, they found that under the inflammatory signal, arid5 will transport from the nucleus to the cytoplasm; in addition, a protein called bimax can produce a high affinity interaction with the NLS sequence of importin-a, thereby inhibiting the CNLS dependent nuclear entry behavior In addition, leptomycin B, an inhibitor of CRM1, can also inhibit the outnucleation of arid5a under the stimulation of LPS   Macrophages can stimulate other immune cells to clear pathogens by secreting inflammatory factors However, too strong inflammation can lead to shock or autoimmune diseases Therefore, how to control the intensity of inflammation becomes very important The researchers focused on the regulation mechanism of IL-6 mRNA by arid5a and regnase-1 Previous studies have shown that arid5a can bind to the 3 'UTR region of IL-6 mRNA, thus inhibiting the RNA degradation process mediated by regnase-1   In addition, the level of inflammatory factors produced by arid5a deficient mice was significantly down regulated, and it also had a high tolerance to shock response Although arid5a plays an important role in immune regulation, it is not clear how arid5a subcellular will regulate immune response   In this study, the authors found that arid5a can produce an exonuclear transport process under the stimulation of LPS Because blocking the outgrowth of arid5a can inhibit the production of IL-6, the authors believe that future research can find new targets for the treatment of Xiuhe or ladder immune diseases.