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작성일 : 18-08-01 10:06
Cyclosporine differentially regulates interleukin-10, interleukin-15, and tumor necrosis factor a production by rheumatoid synoviocytes.
국내/국외 구분: 국외
SCI/SCIE/비SCI 구분: SCI
논문제목: Cyclosporine differentially regulates interleukin-10, interleukin-15, and tumor necrosis factor a production by rheumatoid synoviocytes.
제 1저자, 교신저자: 김호연
나머지 저자: Cho ML, Kim WU, Min SY, Min DJ, Min JK, Lee SH, Park SH, Cho CS, Kim HY.
학술지명: Arthritis and Rheumatism.
Vol(No),페이지:
발행년월일: 2002/01/01
v파일다운로드: 2002/01/01

Abstract

OBJECTIVE:

To determine the direct effect of cyclosporin A (CSA) on the production of cytokines by rheumatoid synovial fibroblasts.

METHODS:

Fibroblast-like synoviocytes (FLS) were prepared from the synovial tissues of patients with rheumatoid arthritis and cultured in the presence of CSA. The production of interleukin-10 (IL-10), IL-15, and tumor necrosis factor a (TNFalpha) by FLS was measured in culture supernatants by enzyme-linked immunosorbent assay. The expression of IL-10, IL-15, and TNFalpha messenger RNA (mRNA) in FLS was determined by polymerase chain reaction (PCR).

RESULTS:

CSA (1-1,000 ng/ml) increased the production of IL-10, but decreased in a dose-dependent manner the levels of IL-15 and TNFalpha that were spontaneously secreted from FLS. CSA also potently inhibited the production of IL-15 and TNFalpha stimulated with interferon-gamma, IL-1beta, or lipopolysaccharide. The inhibitory effect of CSA on IL-15 and TNFalpha production depended on the increase in IL-10, since neutralizing anti-IL-10 antibodies were able to partially reverse this inhibition. In a semiquantitative PCR, CSA increased IL-10 mRNA expression but strongly suppressed IL-1beta-induced IL-15 and TNFalpha mRNA expression, indicating that the production of these cytokines by CSA was regulated at the transcript-xional level. Results with the calcineurin inhibitor FK-506, but not with the immunosuppressant rapamycin, were similar to those with CSA. Agonists of cAMP displayed an additive effect on the changes produced in the IL-10, IL-15, and TNFalpha levels by CSA, while a cAMP antagonist almost completely abrogated the effect of CSA, suggesting that cAMP is the major intracellular signal that mediates cytokine regulation by CSA.

CONCLUSION:

These results suggest that CSA differentially regulates the production of cytokines by rheumatoid synoviocytes via a cAMP-dependent pathway.


 
 

 
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김호연, Cho ML, Kim WU, Min SY, Min DJ, Min JK, Lee SH, Park SH, Cho CS, Kim HY.
Cyclosporine differentially regulates interleukin-10, interleukin-15, and tumor necrosis factor a production by rheumatoid synoviocytes.
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