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Retinoic acid attenuates rheumatoid inflammation in mice.
Kwok, Seung-Ki,Park, Mi-Kyung,Cho, Mi-La,Oh, Hye-Jwa,Park, Eun-Mi,Lee, Dong-Gun,Lee, Jennifer,Kim, Ho-Youn,Park, Sung-Hwan American Association of Immunologists 2012 Journal of Immunology Vol. No.
<P>Retinoic acid is the active vitamin A derivative and is well-known to have diverse immunomodulatory actions. In this study, we investigated the impact of all-trans retinoic acid (ATRA), a biologic key metabolite of vitamin A, on the development of arthritis and the pathophysiologic mechanisms by which ATRA might have antiarthritic effects in animal model of rheumatoid arthritis (RA; collagen-induced arthritis [CIA] in DBA/1J mice). We showed that treatment with ATRA markedly suppressed the clinical and histologic signs of arthritis in the CIA mice. It reduced the expression of IL-17 in the arthritic joints. Interestingly, Foxp3(+) regulatory T cells were markedly increased and IL-17-producing CD4(+) T cells (Th17 cells) were decreased in the spleens of ATRA-treated mice. In vitro treatment with ATRA induced the expression of Foxp3 and repressed the IL-17 expression in the CD4(+) T cells in mice. ATRA suppressed the production of total IgG and IgG2a in splenocytes that were stimulated by LPS. It also reduced serum levels of total IgG and IgG2 anti-collagen Abs and germinal center formation in CIA mice. In addition, the ATRA-treated mice showed decreased osteoclast formation in arthritic joints. Moreover, ATRA downregulated the expression of receptor activator of NF-관B ligand, the leading player of osteoclastogenesis, in the CD4(+) T cells and fibroblast-like synoviocytes from patients with RA. Furthermore, ATRA prevented both human monocytes and mice bone marrow-derived monocytes/macrophage cells from differentiating into osteoclasts. These data suggest ATRA might be an effective treatment modality for RA patients.</P>
Kwok, Seung-Ki,Seo, Soo-Hong,Ju, Ji Hyeon,Yoon, Chong-Hyeon,Park, Soo Chul,Kim, Bum Soo,Kim, Ho-Youn,Park, Sung-Hwan The Korean Academy of Medical Sciences 2008 JOURNAL OF KOREAN MEDICAL SCIENCE Vol.23 No.1
<P>Cryptococcal meningitis is a rare complication of systemic lupus erythematosus (SLE). The nonspecific neurologic findings associated with this infection delays accurate diagnosis because initial neuropsychiatric manifestations of SLE are in instances indistinguishable from that of crytococcal meningitis. We report a case of cryptococcal meningitis presenting with unilateral sixth cranial nerve palsy in a male patient with SLE, which was successfully treated with antifungal agents.</P>
New insights into the role of renal resident cells in the pathogenesis of lupus nephritis
( Seung-ki Kwok ),( George C. Tsokos ) 대한내과학회 2018 The Korean Journal of Internal Medicine Vol.33 No.2
Systemic lupus erythematosus (SLE), an autoimmune disease of unknown etiology, is characterized by the production of autoantibodies and end-organ damage. Lupus nephritis affects up to 70% of patients with SLE and is the most critical predictor of morbidity and mortality. The immunopathogenesis of SLE is complex and most clinical trials of biologics targeting immune cells or their mediators have failed to show efficacy in SLE patients. It has therefore become increasingly clear that additional, local factors give rise to the inflammation and organ damage. In this review, we describe recent advances in the role of renal resident cells, including podocytes, mesangial cells, and epithelial cells, in the pathogenesis of lupus nephritis.
( Seung In Paek ),( Seung Min Jung ),( Jennifer Lee ),( Seung-ki Kwok ),( Wan-uk Kim ),( Sung-hwan Park ),( Ji Hyeon Ju ),( Kyeong-yae Sohng ) 대한류마티스학회 2018 대한류마티스학회지 Vol.25 No.4
Objective. To examine effects of an individual education program using the treating rheumatoid arthritis to target (RA T2T) strategy in patients with moderate-severe rheumatoid arthritis. Methods. Patients were assigned randomly to an educational intervention (n=33) or conventional care group (n=33). The intervention was a nurse-delivered 9-month educational program consisting of 3 monthly sessions and monthly telephone counseling. The assessments occurred at the baseline and every 3 months in both groups, but only the intervention group completed the 9-month education follow-up. The outcome variables included the disease activity (DAS28), functional disability (KHAQ), fatigue (FACIT-Fatigue), and quality of life (SF-36). Repeated measures ANOVA and a Bonferroni multiple comparison were used to evaluate the outcome variables comparing the groups and follow-up times. Results. Significant interactions were observed between the groups and follow-up times in the disease activity (p=0.041), fatigue (p=0.042), and physical (p=0.006) and mental (p=0.031) health-related quality of life, but there was no significant interaction in the functional disability (p=0.110). Significant differences were noted between the groups at the 9-month period (p=0.048) in disease activity and fatigue, and at the 6-month (p=0.023) and 9-month periods (p=0.027) in the physical health-related quality of life. Conclusion. This education program using the RA T2T strategy had significant benefits on the disease activity, fatigue, and quality of life in patients with moderate to severe rheumatoid arthritis, and the results suggested that this contributed to positive clinical outcomes as a good practical nursing intervention. (J Rheum Dis 2018;25:255-262)
Kwok, Seung-Ki,Cho, Mi-La,Her, Yang-Mi,Oh, Hye-Joa,Park, Mi-Kyung,Lee, Seon-Yeong,Woo, Yun Ju,Ju, Ji Hyeon,Park, Kyung-Su,Kim, Ho-Youn,Park, Sung-Hwan BioMed Central 2012 ARTHRITIS RESEARCH AND THERAPY Vol.14 No.2
<P><B>Introduction</B></P><P>The study was undertaken to investigate the interrelation of toll-like receptor (TLR) and interleukin (IL)-17 in the salivary glands of patients with primary Sjogren's syndrome (pSS) and to determine the role of TLR and IL-17 in the pathophysiology of pSS.</P><P><B>Methods</B></P><P>The expressions of various TLRs, IL-17 and the cytokines involved in Th17 cell differentiation including IL-6, IL-23, tumor necrosis factor-alpha (TNF-α) and IL-1β were examined by immunohistochemistry in salivary glands of pSS patients. The IL-17 producing CD4+ T cells (Th17 cells) were examined by flow cytometry and confocal staining in peripheral mononuclear blood cells (PMBCs) and salivary glands of pSS patients. After PBMCs were treated with TLR specific ligands, the induction of IL-17 and IL-23 was determined using real-time PCR and ELISA. The signaling pathway that mediates the TLR2 stimulated production of IL-17 and IL-23 was investigated by using treatment with specific signaling inhibitors.</P><P><B>Results</B></P><P>We showed that TLR2, TLR4, TLR6, IL-17 and the cytokines associated with Th17 cells were highly expressed in salivary glands of pSS patients but not in controls. The expressions of TLR2, TLR4 and TLR6 were observed in the infiltrating mononuclear cells and ductal epithelial cells, whereas IL-17 was mainly observed in infiltrating CD4+ T cells. The number of IL-17 producing CD4+ T cells was significantly higher in pSS patients both in PBMCs and minor salivary glands. The stimulation of TLR2, TLR4 and TLR6 additively induced the production of IL-17 and IL-23 from the PBMCs of pSS patients especially in the presence of TLR2 stimulation. IL-6, signal transducer and activator of transcription 3 (STAT3) and nuclear factor-kappaB (NF-kB) pathways were implicated in the TLR2 stimulated IL-17 and IL-23.</P><P><B>Conclusions</B></P><P>Our data demonstrate that TLR2 ligation induces the production of IL-23/IL-17 via IL-6, STAT3 and NF-kB pathway in pSS. Therefore, therapeutic strategies that target TLR/IL-17 pathway might be strong candidates for treatment modalities of pSS.</P>