http://chineseinput.net/에서 pinyin(병음)방식으로 중국어를 변환할 수 있습니다.
변환된 중국어를 복사하여 사용하시면 됩니다.
Cytokine의 세포 내 신호전달 과정의 억제 기전 (Jak-STAT Signaling을 중심으로)
지종대 ( Jong Dae Ji ),이영호 ( Young Ho Lee ),송관규 ( Gwan Gyu Song ) 대한류마티스학회 2003 대한류마티스학회지 Vol.10 No.1
Cytokines are secreted proteins and interact with their specific cell surface receptors, triggering intracellular signal transduction pathways that activate a number of genes crucial for the biological functions of cytokines. These cytokine signal transduction pathways are tightly regulated processes. The negative regulations of cytokine signaling are achieved by receptor internalization and degradation, dephosphorylation of signaling intermediates, expression of protein inhibitors such as suppressor of cytokine signaling (SOCS) and protein inhibitors of activated STAT (PIAS). The observation that cytokines are central to the inflammatory and destructive process in several autoimmune diseases suggests that interventions targeting the cytokine intracellular signaling will be a new therapeutic strategy in autoimmune diseases. We review the current knowledge about negative regulation of cytokine signal transduction.
Network Analysis을 이용한 류마티스관절염 활액 대식세포에서 유전자 발현 연구
지종대 ( Jong Dae Ji ),김태환 ( Tae Hwan Kim ),이빛나라 ( Bit Na Ra Lee ),최성재 ( Sung Jae Choi ),이영호 ( Young Ho Lee ),송관규 ( Gwan Gyu Song ) 대한류마티스학회 2011 대한류마티스학회지 Vol.18 No.2
Objective. We wanted to investigate the mechanisms that could account for the pathogenesis of rheumatoid arthritis, so we examined the different expressions of the genes in rheumatoid arthritis (RA) synovial fluid macrophages as compared with that of normal peripheral blood (PB) monocyte-derived macrophages using microarray and bioinformatic analysis. Methods. We examined the expression of genes by using a gene expression oligonucleotide microarray. The differences of the gene expressions between the RA synovial macrophages and the normal PB monocytes-derived macrophages were analyzed using bioinformatic tools, including cytoscape and its plugin. Results. In this study, we found that 899 genes (464 genes up-regulated and 435 genes down-regulated) were differentially expressed between the two groups. Among the 899 genes, 552 genes were included for gene ontology analysis and network analysis. Based on biological process ontology, they were categorised mainly into immune response processes, responses to stimulus and signaling and regulation of biological processes. In addition to the genes related with STAT1 and AP-1 signaling, we found that the genes involved in the antigen processing and the cell cycle are abundantly expressed in RA synovial macrophages, suggesting that these genes may play an important role in the pathogenesis of RA. Conclusion. Our study suggest that this approach using integration of the gene expression profile with the protein interaction data may help to find several important pathogenic mechanisms in RA.
인간 대식세포에서 1,25(OH)2D3에 의한 CYP24 유전자 발현에 있어 MAPK의 역할
지종대 ( Jong Dae Ji ),이빛나라 ( Bit Na Ra Lee ),김태환 ( Tae Hwan Kim ),우진현 ( JIn Hyun Woo ),최성재 ( Sung Jae Choi ),이영호 ( Young Ho Lee ),송관규 ( Gwan Gyu Song ) 대한류마티스학회 2010 대한류마티스학회지 Vol.17 No.3
Objective: Several important roles of 1,25(OH)2D3 have been recognized in the immune system. The availability of 1,25(OH)2D3 at the cellular level is significantly influenced by the relative abundance of enzymes to synthesize (CYP27B1) and catabolize (CYP24) 1,25(OH)2D3. In this study, we examined the effect of 1,25(OH)2D3 on the expression of the CYP24 gene and the role of MAPK for the induction of CYP24 by 1,25(OH)2D3 in activated human macrophages. Methods: For obtaining human activated macrophages, we treated U937 cells with PMA and we cultured these cells for 24 hours to adhere. After 24 hours treatment with PMA, the differentiated cells were washed with phosphate buffered saline (PBS), and then they were used for examining the effect of 1,25(OH)2D3 on the expression of the CYP24 gene. The mRNA expressions of the vitamin-D3 inducible genes were measured by real-time PCR, and the change of the protein expression by 1,25(OH)2D3 was measured by immunoblotting. Results: 1,25(OH)2D3 significantly induced the expression of CYP24 in the U937 cells and the 1,25(OH)2D3-induced expression of CYP24 was strongly augmented in the PMA-differentiated U937 cells. The 1,25(OH)2D3-induced expression of CYP24 was mediated by Erk1/2 and p38 MAPKs. Parallel to the induced expression of CYP24, 1,25(OH)2D3 induced the expression and phosphorylation of the CCAAT enhancer-binding protein (C/EBPβ). Conclusion: In this study, we found that 1,25(OH)2D3 inducedthe expression of CYP24 via activation of MAPKs. These results suggest that MAPK inhibitors may be useful for the treatment of inflammatory conditions, in which active vitamin D3 can be used as the therapeutic molecule, by increasing the availability of 1,25(OH)2D3.
지종대 ( Jong Dae Ji ),김태환 ( Tae Hwan Kim ) 대한류마티스학회 2010 대한류마티스학회지 Vol.17 No.3
MicroRNAs (miRNAs) are small, single-stranded, non-coding RNA molecules of 20∼22 nucleotides, which are involved in many biologic functions such as development, cell proliferation, differentiation, and apoptosis. In addition to these biologic functions, recent reports have demonstrated that miRNAs play important roles in the development of the immune system and the regulation of immune responses. Dysregulation of miRNAs might be involved in the pathogenesis of autoimmune diseases such as rheumatoid arthritis (RA). Recent studies have shown that miR-146a, miR-155, and miR-203 are overexpressed in RA and that miR-124a is under expressed in RA. miR-146 downregulates the expression of IL-1 receptor associated kinase 1 and TNF receptor-associated factor 6 involved in IL-1β signaling, and miR-155 suppresses the expression of matrix metalloproteinases 1 and 3, suggesting that these miRNAs act as negative feedback regulators of inflammation and tissue damage in RA. In this report, we review the current knowledge about miRNAs and summarize the involvement of miRNAs in RA.
지종대 ( Jong Dae Ji ),유대현 ( Dae Hyun Yoo ) 대한류마티스학회 2001 대한류마티스학회지 Vol.8 No.1
Rheumatoid arthritis is characterized by a chronic inflammatory synovitis, eventually leading to destruction of bone and cartilage. Significant hyperplasia and infiltration of activated inflammatory cells play a major role in the destruction of joint. The proliferation of synovial cells could be derived from imbalance between apoptotic cell death and excessive proliferation of synovial cells. However, many reports regarding on the apoptosis or proliferation of synovial cells showed a little bit contradictory up to date. Induction of synovial cell apoptosis could be an interesting and attractive way of treatment by way of many signal transduction pathway, such as NFkB, P53, sentrin, FADD, etc. We discussed on the apoptosis and proliferation of synovial cells, and focused on the proposed mechanisms of resistance for apoptosis. Here, we reviewed literatures on the apoptosis and abnormal proliferation of synovial cells, and focused on the proposed mechanisms of resistance against apoptosis. In addition, we mentioned about the possibility of apoptosis induction as a modality of treatment against rheumatoid arthritis in future.