http://chineseinput.net/에서 pinyin(병음)방식으로 중국어를 변환할 수 있습니다.
변환된 중국어를 복사하여 사용하시면 됩니다.
류마티스관절염 활막세포에서 NF-κB 신호전달을 통한 MIF의 SDF-1 생성 유도
조미라(Cho, Mi-La),박미경(Park, Mi-Kyung),김경운(Kim, Kyoung-Woon),오혜좌(Oh, Hye-Jwa),이선영(Lee, Seon-Yeong),박진실(Park, Jin-Sil),허유정(Heo, Yu-Jung),주지현(Ju, Ji-Hyeon),민준기(Min, Jun-Ki),이상헌(Lee, Sang-Heon),박성환(Park, Su 대한면역학회 2007 Immune Network Vol.7 No.1
Stromal cell-derived factor (SDF)-1 is a potent chemoattractant for activated T cells into the inflamed Rheumatoid arthritis (RA) synovium. To determine the effect of macrophage migration inhibitory factor (MIF) on the production of SDF-1 in the inflamed RA synovium. Methods: The expression of SDF-1 and MIF in RA and Osteoarthritis (OA) synovium was examined by immunohistochemical staining. The SDF-1 was quantified by RT-PCR and ELISA after RA fibroblast like synoviocyte (FLS) were treated with MIF in the presence and absence of inhibitors of intracellular signal molecules. The synovial fluid (SF) and serum levels of MIF and SDF-1 in RA, OA and healthy control were measured by ELISA. Results: Expression of SDF-1 and MIF in synovium was higher in RA patients than in OA patients. The production of SDF-1 was enhanced in RA FLS by MIF stimulation. Such effect of MIF was blocked by the inhibitors of NF-κB . Concentrations of SDF-1 in the serum and SF were higher in RA patients than in OA patients and healthy control. SDF-1 and MIF was overexpressed in RA FLS, and MIF could up-regulate the production of SDF-1 in RA FLS via NF-κB -mediated pathways. Conclusion: These results suggest that an inhibition of interaction between MIF from T cells and SDF-1 of FLS may provide a new therapeutic approach in the treatment of RA.
류마티스관절염 활막세포에서 NF-${\kappa}B$ 신호전달을 통한 MIF의 SDF-1 생성 유도
조미라,박미경,김경운,오혜좌,이선영,박진실,허유정,주지현,민준기,이상헌,박성환,김호연,Cho, Mi-La,Park, Mi-Kyung,Kim, Kyoung-Woon,Oh, Hye-Jwa,Lee, Seon-Yeong,Park, Jin-Sil,Heo, Yu-Jung,Ju, Ji-Hyeon,Min, Jun-Ki,Lee, Sang-Heon,Park, Sung-Hwa 대한면역학회 2007 Immune Network Vol.7 No.1
Background: Stromal cell-derived factor (SDF)-1 is a potent chemoattractant for activated T cells into the inflamed Rheumatoid arthritis (RA) synovium. To determine the effect of macrophage migration inhibitory factor (MIF) on the production of SDF-1 in the inflamed RA synovium. Methods: The expression of SDF-1 and MIF in RA and Osteoarthritis (OA) synovium was examined by immunohistochemical staining. The SDF-1 was quantified by RT-PCR and ELISA after RA fibroblast like synoviocyte (FLS) were treated with MIF in the presence and absence of inhibitors of intracellular signal molecules. The synovial fluid (SF) and serum levels of MIF and SDF-1 in RA, OA and healthy control were measured by ELISA. Results: Expression of SDF-1 and MIF in synovium was higher in RA patients than in OA patients. The production of SDF-1 was enhanced in RA FLS by MIF stimulation. Such effect of MIF was blocked by the inhibitors of NF-${\kappa}B$. Concentrations of SDF-1 in the serum and SF were higher in RA patients than in OA patients and healthy control. SDF-1 and MIF was overexpressed in RA FLS, and MIF could up-regulate the production of SDF-1 in RA FLS via NF-${\kappa}B$-mediated pathways. Conclusion: These results suggest that an inhibition of interaction between MIF from T cells and SDF-1 of FLS may provide a new therapeutic approach in the treatment of RA.
류마티스관절염 환자의 활액 세포에서 IL-17과 $IL-1{\beta}$에 의한 IL-23p19의 발현 증가
조미라,허유정,오혜좌,강창민,이선영,홍연식,김호연,Cho, Mi-La,Heo, Yu-Jung,Oh, Hye-Jwa,Kang, Chang-Min,Lee, Seon-Yeong,Hong, Yeon-Sik,Kim, Ho-Youn 대한면역학회 2008 Immune Network Vol.8 No.1
Interleukin-23 (IL-23) is a novel pro-inflammatory cytokine which has been implicated to play a pathogenic role in rheumatoid arthritis (RA). This study was undertaken to investigate the IL-23 inductive activity of the proinflammatory cytokine IL-17, $IL-1{\beta}$ and tumor necrosis factor (TNF-${\alpha}$) in RA synovial fluid mononuclear cells (SFMC). Expression of IL-23p19, IL-17, $IL-1{\beta}$ and TNF-${\alpha}$ in joint was examined by immunohistochemistry (IHC) of patients with RA and osteoarthritis (OA). The effects of IL-17 and $IL-1{\beta}$ on expression of IL-23p19 in human SFMC from RA patients were determined by reverse transcriptase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA). IL-23p19 was expressed in the RA fibroblast like synoviocyte (FLS), but not from OA FLS. Similar to the protein expression, IL-23p19 mRNA could be detected by RT-PCR in RA SFMC. IL-17 and $IL-1{\beta}$ could induce RA SFMC to produce the IL-23p19. The effects of IL-17 were much stronger than $IL-1{\beta}$ or TNF-${\alpha}$. These responses were observed in a doseresponsive manner. In addition, IL-17 or $IL-1{\beta}$ neutralizing antibody down-regulated the expression of IL-23p19 induced by LPS in RA-SFMC. Our results demonstrate that IL-23p19 is overexpressed in RA synovium and IL-17 and $IL-1{\beta}$ appears to upregulate the expression of IL-23p19 in RA-SFMC.
조미라,허유정,박진실,이선영,성영철,김호연,Cho, Mi-La,Heo, Yu-Jung,Park, Jin-Sil,Lee, Seon-Yeong,Sung, Young-Chul,Kim, Ho-Youn 대한면역학회 2007 Immune Network Vol.7 No.1
Autoimmune arthritis, such as rheumatoid arthritis (RA), is a chronic inflammatory disorder that primarily affects the joints and then results in their progressive destruction. Effector Th cells have been classified as Th1 and Th2 subsets based on their cytokine expression profiles and immune regulatory function. Another subset of T cells termed Th17 was recendy discovered and known to selectively produce IL-17. Also, Th17 was shown to be generated by TGF${\beta}$ and IL-6 and maintained by IL-23. IL-17 is a proinflammatory cytokine that is considered to involve the development of various inflammatory autoimmune diseases such as RA, asthma, lupus, and allograft rejection. IL-17 is present in the sera, synovial fluids and synovial biopsies of most RA patient. IL-17 activates RA synovial fibroblasts to synthesize IL-6, IL-8 and VEGF via PI3K/Akt and NF-${\kappa}B$ dependent pathway. IL-17 increases IL-6 production, collagen destruction and collagen synthesis. In addition, it not only causes bone resorption but also increases osteoclastogenesis and fetal cartilage destruction. Inhibition of the IL-17 production may contribute a novel therapeutic approach along with potent anti-inflammatory effect and with less immunosuppressive effect on host defenses.
류마티스 관절염 환자에서 Conserved T 세포 수용체의 CDR3 motif를 표현하는 제2형 콜라겐 특이 T세포주의 형성과 유지
김승훈,조미라,윤지희,박성환,조철수,황수연,김호연,Kim, Seung-Hoon,Cho, Mi-La,Youn, Jeehee,Park, Sung-Hwan,Hwang, Sue-Yun,Cho, Chul-Soo,Kim, Ho-Youn 대한면역학회 2001 Immune Network Vol.1 No.1
Background: To determine the molecular structure of type II collagen-specific T-cell receptors associated with rheumatoid arthritis (RA). Methods: We generated CII-specific T-cell lines of 8 RA patients by prolonged in vitro culture with bovine CII (bCII) and the immunogenic peptide (256-270) of human CII. The proliferation response towards CII stimulation was measured from the uptake of 3H-thymidine. Changes in the secretion of Th 1 and Th2 cytokines in the culture supernatent were measured by ELISA. The TCR clonotypes of these T-cells were examined by RT-PCR/SSCP analyses of all 22 $V_{\beta}$ chains. Results: T-cells from patients' tissue exhibited strong proliferation index upon CII stimulation, which was maintained up to 6 months in the culture. The secretion of INF-$\gamma$from these T-cells increased along with the duration of culture time, while the amount of IL-4 production did not show significant changes. The SSCP band patterns of patients' T-cells appear as discrete bands unlike the smeary streak produced from normal samples. Some SSCP bands, each representing selected expansion of a TCR containing certain subtype of $V_{\beta}$ peptides, appeared to be identical in more than one patients. Among these, the expansion of SSCP band representing the $V_{\beta}$ 14 CDR3 region persisted after switching the antigen to the immunogenic human peptide (256-270). Conclusion: CII-reactive T-cells expressing distinct CDR3 motifs are selectively expanded in the peripheral blood and synovial fluid of RA patients, and their persistent proliferation upon CII stimulation, as well as the production Th 1-type cytokines, may play pivotal roles in RA pathogenesis.
콜라겐 유도 관절염에서 콜라겐 항원 특이 $V{\beta}3$+CD4+T 세포의 선택적 증식
이재선,조미라,이정은,민소연,윤종현,김완욱,민준기,박성환,김호연,Lee, Jae-Seon,Cho, Mi-La,Lee, Jung-Eun,Min, So-Youn,Yoon, Chong-Hyeon,Kim, Wan-Uk,Min, Jun-Ki,Park, Sung-Hwan,Kim, Ho-Youn 대한면역학회 2005 Immune Network Vol.5 No.2
Background: Collagen-induced arthritis (CIA) in mice is animal model of autoimmune disease known as rheumatic arthritis in human. We investigated CII-specific CD4+ T cell receptor usage in CIA mice. Methods: In CIA model, draining lymph node (dLN) CD4+ T cells and splenocytes at $3^{rd},\;5^{th},\;8^{th}$ week, we investigated CII-specific T cell proliferation, production of IL-17, IFN-${\gamma}$, TNF-${\alpha}$, IL-4 and IL-10. And we also performed anti-CII IgG Ab measurements in serum level, TCRV ${\beta}$ usage and T cell clonality with RT-PCR-SSCP analysis. Also, we performed proliferative response against CII when CII-specific T cell subset is deleted. Results: CIA mice showed more increase in the serum level of anti-CII IgG than normal mice after induction of arthritis. And the level of anti-CII IgG2a in CIA mice was increased after $3^{rd}$ week after primary immunization, while anti-CII IgG1 was decreased. Draining LN CD4+ T cells have proliferated against CII stimulation at $3^{rd}$ week after $1^{st}$immunization. CD4+T cells derived from dLN of CIA mice produced proinflammatory cytokine IFN-${\gamma}$, IL-17 etc. Draining LN CD4 T cells of CIA presented higher proportion of CD4+V ${\beta}3$+subset compared to those of normal mice at $3^{rd}$ week after $1^{st}$ immunization, and they were increased in proportion by CII stimulation. Draining LN CD4+ T cells without TCRV ${\beta}3+/V{\beta}8.1/8.2+/V{\beta}$10b+cells were not responsive against CII stimulation. But, CII-reactive response of TCRV ${\beta}3-/V{\beta}8.1/8.2-/V{\beta}$10b- T cells was recovered when $V{\beta}3+$ T cells were added in culture. Conclusion: Our results indicate that CD4+$V{\beta}3+$ T cells are selectively expanded in dLN of CIA mice, and their recovery upon CII re-stimulation in vitro, as well as the production Th1-type cytokines, may play pivotal role in CIA pathogenesis.
Estrogen이 전신홍반루푸스 환자 B세포의 DNA Methylation에 미치는 영향
박미경 ( Mi Kyung Park ),박성환 ( Sung Hwan Park ),곽승기 ( Seung Ki Kwok ),조미라 ( Mi La Cho ),김호연 ( Ho Youn Kim ) 대한류마티스학회 2007 대한류마티스학회지 Vol.14 No.1
Objective: Epigenetics is an important, alternative mechanism of gene regulation that is independent of the nucleotide sequences of DNA. We investigated mRNA levels for DNA methyltransferase-1 (DNMT-1), and the effect of estrogen on the expression of DNMT-1 level in T cells and B cells from patients with systemic lupus erythematosus (SLE) and healthy subjects, and assessed the possible etiological role of DNA methylation in the pathogenesis of SLE. Methods: mRNA levels for DNMT-1 in CD4+ T cells and CD19+ B cells from 37 patients with SLE and 12 healthy controls were examined using RT-PCR. We used specific primer for DNMT-1 and β actin, The effect of estrogen on the DNA methylation was measured by the mRNA level of DNMT-1 CD4+ T cells and CD19+ B cells treated with 100 nM of 17 β-estradiol for 72 hour. Results: The levels of DNMT-1 mRNA were significantly lower in CD4+ T cells and CD19+ B cells from SLE patients compared with healthy controls. We observed the suppression of the levels of DNMT-1 mRNA by stimulated with estrogen in patients with SLE patients, especially in CD19+B cells. DNA hypomethylation of B cells was tend to be correlated with the level of anti-ds DNA antibody without statistical significance (r=-0.43, p=0.3). Conclusion: Our observations suggest that suppression of DNMT-1 by estrogen in B cells from patients with SLE might be related to the pathogenesis of SLE. Epigenetic studies may provide clues for developing new treatment strategies of SLE.
박민정,Mi-La Cho,Hyun-Sil Park,Hye-Joa Oh,윤보영,임정연,조미라,조석구 생화학분자생물학회 2012 Experimental and molecular medicine Vol.44 No.11
IL-17-producing CD4+ T cells (Th17) play important functions in autoimmune diseases and allograft rejection of solid organs. We examined the effects of IL 17 and its mechanism of action on arthritis in a murine collagen-induced arthritis (CIA) model using bone marrow transplantation (BMT) system. DBA/1J mice were administered a lethal radiation dose and then rescued with bone marrow derived from either wild-type (WT) or IL-17-/- mice on C57BL/6 background mice. CIA was induced after the bone marrow transplant, and disease progression was characterized. DBA/1J mice with CIA that received IL-17-/- donor bone marrow showed potently inhibited development and severity of clinical arthritis as compared with CIA mice that received WT bone marrow. Reduced secretion of the pro-inflammatory cytokines tumor necrosis factor-α,IL-1β, and IL-6, and collagen-specific T cell responses were observed in mice that received IL-17-/- bone marrow. IL-17 blockade also inhibited effector T cell proliferation by reciprocally regulating the Treg/Th17ratio. IL-17 blockade prevented joint destruction in mice with CIA. These findings suggest that CIA with BMT is a viable method of immunological manipulation and that IL-17 deficiency suppresses severe joint destruction and inflammation in CIA mice. There may be clinical benefits in blocking IL-17 and BMT in the treatment of rheumatoid arthritis.