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작성일 : 18-08-22 10:52
IL-1 receptor antagonist (IL-1Ra)-Fc ameliorate autoimmune arthritis by regulation of the Th17 cells/Treg balance and arthrogenic cytokine activation.
국내/국외 구분: 국외
SCI/SCIE/비SCI 구분: SCI
논문제목: IL-1 receptor antagonist (IL-1Ra)-Fc ameliorate autoimmune arthritis by regulation of the Th17 cells/Treg balance and arthrogenic cytokine activation.
제 1저자, 교신저자:
나머지 저자: Lee SY, Min HK, Lee SH, Kwok SK, Ju JH, Cho ML, Park SH.
학술지명: Immunology Letters
Vol(No),페이지:
발행년월일:
v파일다운로드:

Abstract

INTRODUCTION:

IL-1β signalling has a critical role in the pathogenesis of various types of inflammatory arthritis including rheumatoid arthritis (RA). We aimed to investigate the therapeutic effects of human IL-1 receptor antagonist with Fc fragment (hIL-1Ra-Fc) on autoimmune arthritis and to identify the possible mechanisms by which hIL-1RA-Fc exerts anti-arthritic effects in a murine model of RA and patients with rheumatoid arthritis.

METHODS:

Collagen-induced arthritis (CIA) murine model was established in DBA/1J mice. The levels of various cytokines were determined by using enzyme-linked immunosorbent assay. The mouse joints were assessed for clinical arthritis score and histologic features. Th17 cells and Treg cells were stained by using antibodies specific for CD4, IL-17, CD25, and FoxP3. Osteoclastogenesis was determined by TRAP staining and real-time PCR.

RESULTS:

hIL-1RA-Fc reduced the arthritis incidence, histological inflammation and cartilage score in the CIA model. The expression of proinflammatory cytokines, VEGF and RANK, was reduced in the affected joint of hIL-1Ra-Fc-treated mice. hIL-1Ra-Fc-treated mice showed decreased number of Th17 cells with increased number of Treg cells in spleens. hIL-1Ra-Fc reduced Th17 cell differentiation by inactivation of STAT3 signalling, and reciprocally induced Treg cell differentiation through STAT5 signalling. In addition, the expression of IL-17, TNF-α, RANKL, and VEGF was decreased, while Foxp3 gene expression was increased in PBMCs of RA patients after administration of hIL-1Ra-Fc.

CONCLUSION:

The anti-arthritis effects of hIL-1RA-Fc are associated with regulation of balance between Th17 cells and Treg cells and suppression of osteoclastogenesis and angiogenesis in the affected joints.


맛있다1 19-05-07 10:36
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