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KMID : 0388220140210030122
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Journal of the Korean Rheumatism Association
2014 Volume.21 No. 3 p.122 ~ p.131
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DICAM-mediated Inhibition of Type 1 Interferon System during Macrophage Differentiation of THP-1 Cells
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Kim Bo-Yeon
Park In
Jung Youn-Kwan
Han Min-Su
Kim Kun-Woo
Han Seung-Woo
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Abstract
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Objective: We have previously shown that DICAM inhibits LPS-mediated macrophage differentiation. However, less is known about the exact action mechanisms of DICAM on the macrophage function and differentiation.
Methods: To induce differentiation into a resting M0 mac-rophage, THP-1 cells were cultured with 100 nM PMA for 24 h, and then rested for 3 days. THP-1 cells were infected with 50 moi of control LacZ- or DICAM-containing adenovirus. The RNA expression profile associated with DICAM during THP-1 differentiation was analyzed with a microarray chip and in silico analysis with Ingenuity Pathway Analysis (IPA) program.
Results: A disease and function analysis of the microarray data in DICAM-overexpressed THP-1 cells revealed a sup-pression in the expression of multiple genes involved in the response of myeloid cells and phagocytes, and an increase of genes associated with apoptosis of fibroblast cell-line, and viral infection and replication. The canonical pathway anal-ysis also showed the most prominent changes of signaling pathways that involve inflammation responses. An upstream regulator analysis identifyingmolecules upstream of the genes that potentially explain the observed expression changes revealed that IRF7 and the genes in type 1 interfer-on system, such as IFNA2 and IFNAR,was significantly at-tenuated by DICAM. A mechanistic network analysis con-firmed a direct causal association between IRF7 and type 1 interferon system. A real-time RT-PCR analysis validat-ing the microarray data verified the significant suppression of IRFs, IFNA2, and IFNB1.
Conclusion: These results suggest that DICAM can be a critical regulator of type 1 interferon system, which is an essential mediator in the process of intracellular infection and systemic lupus erythematosus.
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KEYWORD
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DICAM, Interferon, Interferon regulatory fac-tor, Macrophage, THP-1
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