Rheumatoid Arthritis: Hsu YH

Wei CC, Hsu YH, Li HH, Wang YC, Hsieh MY, Chen WY, Hsing CH, Chang MS. · Institute of Basic Medical Sciences, Medical College, National Cheng Kung University, Tainan, Taiwan. · J Biomed Sci. · Pubmed #16703417 No free full text.

Abstract: IL-20 belongs to the IL-10 family and plays a role in skin inflammation and the development of hematopoietic cells. Little is known about its other biological functions and clinical implications, however. Updated information about IL-20, such as its identification, expression, receptors, signaling, biological activities, and potential clinical implications, is illustrated in this review based on our research and on data available in the literature. Our studies of IL-20 show that it is a pleiotropic cytokine with potent inflammatory, angiogenic, and chemoattractive characteristics. Inflammation and angiogenesis are essential for the pathogenesis of rheumatoid arthritis and atherosclerosis. Based on in vitro data and clinical samples, we demonstrated that IL-20 is involved in the diseases of rheumatoid arthritis and atherosclerosis. In addition, we found in our studies that IL-20 signaled through different molecules in several cells. The present review presents the clinical implications of IL-20 in rheumatoid arthritis and atherosclerosis. It may provide new therapeutic options in the future.

Yu SF, Cheng TT, Hsu YH, Lai HM, Chen YC, Chiu CK, Lin KM, Chang C, Chen CJ, Kang HY. · Graduate Institute of Clinical Medical Sciences, Chang Gung University, 16F-4, No. 123-9, Ta-Pei Road, Niao-Sung Hsiang, 833, Kaohsiung Hsein, Taiwan. · Clin Rheumatol. · Pubmed #17431729 No free full text.

Abstract: We investigated the relationship between CAG and GGC repeat polymorphism of the androgen receptor (AR) gene and rheumatoid arthritis (RA) in female patients with different disease subtypes. This case-control study enrolled 215 women in three groups: RA patients refractory to standardized therapy (n = 51); RA patients at complete remission phase (n = 60); and healthy controls (n = 104). CAG and GGC repeat lengths were determined by automated fluorescence-based DNA fragment-sizing method. Demographic data, allele lengths, allele distribution, and zygosity status of CAG/GGC repeats were assessed for the three groups. Refractory RA patients tend to have a significantly younger onset age of RA and more elevated erythrocyte sedimentation rates than do remission RA patients. Mean and median values of CAG and GGC repeat lengths are similar in both RA and control patients. However, RA patients harboring any long CAG alleles with more than 23 repeats had an increased risk of a refractory course, whereas differences in risk were not observed between these patients and RA subtypes harboring any long GGC alleles with more than 16 repeats. In addition, the homozygous frequency of CAG but not GGC alleles was lower in refractory RA than in remission RA patients or in controls (p = 0.042). Neither CAG nor GGC repeat lengths had a significant relationship with rheumatoid factor reactivity. Our observations indicate that short CAG repeats of the AR gene with higher transactivation activity may have protective effects against refractory course of RA development and that homozygous frequency of CAG alleles may be involved in the disease remission subtype. In contrast, lack of association of GGC polymorphism and RA was also observed. Together, these data imply that CAG but not GGC alleles in the AR polymorphism may play an important role in modulating the disease pattern of RA among Taiwanese women.

Hsu YH, Li HH, Hsieh MY, Liu MF, Huang KY, Chin LS, Chen PC, Cheng HH, Chang MS. · National Cheng Kung University, Tainan, Taiwan. · Arthritis Rheum. · Pubmed #16947773 links to  free full text

Abstract: OBJECTIVE: The pathogenesis of rheumatoid arthritis (RA) reflects an ongoing imbalance between proinflammatory and antiinflammatory cytokines. Interleukin-20 (IL-20) has proinflammatory properties for keratinocytes. In this study, we sought to determine whether IL-20 is involved in RA. METHODS: We analyzed IL-20 levels in synovial fluid from RA patients. IL-20 and its receptors were detected in RA synovial fibroblasts (RASFs), using immunohistochemical staining. The effect of IL-20 on endothelial cells, neutrophils, and RASFs was investigated using MTT and migration assays. The expression of IL-20 and its receptors in healthy rats and in rats with collagen-induced arthritis (CIA) was also analyzed. Soluble IL-20 receptor type I (sIL-20RI) or sIL-20RII was administered to rats with CIA by intramuscular electroporation, and the severity of arthritis was monitored. RESULTS: RA patients expressed significantly higher levels of synovial fluid IL-20 than did the rheumatic disease controls. IL-20 and its receptors were expressed in the synovial membranes and RASFs. IL-20 induced RASFs to secrete monocyte chemoattractant protein 1, IL-6, and IL-8, and it promoted neutrophil chemotaxis, RASF migration, and endothelial cell proliferation. Both IL-20 and IL-20RI were up-regulated in the rat CIA model. In vivo, electroporated sIL-20RI plasmid DNA decreased the severity of arthritis in the rats with CIA. CONCLUSION: IL-20 was up-regulated in the synovial fluid of RA patients and acted as a chemokine that attracted the migration of neutrophils and RASFs in vitro. The rat CIA model demonstrated that IL-20 was involved in the pathogenesis of arthritis, because sIL-20RI significantly reduced arthritis in rats with CIA. Thus, IL-20 may modulate the incidence and severity of arthritis and play important roles at local sites of inflammation.