The effect of sulfasalazine on rheumatoid arthritic synovial tissue chemokine production.
The effect of sulfasalazine on rheumatoid arthritic synovial tissue chemokine production.
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DOI：
10.1006/exmp.2002.2460
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发表时间：
2002-10
影响因子：
3.6
通讯作者：
M. Volin;P. Campbell;M. A. Connors;D. Woodruff;A. Koch
中科院分区：
文献类型：
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作者：
M. Volin;P. Campbell;M. A. Connors;D. Woodruff;A. Koch
类风湿关节炎(RA)是一种侵袭性炎症性疾病，趋化因子被认为能募集白细胞并诱导血管生成。本研究采用酶联免疫吸附试验和流式细胞术观察柳氮磺胺吡啶(SASP)及其代谢产物磺胺吡啶(SP)和5-氨基水杨酸(5ASA)对RA滑膜组织外植体和IL-1β刺激的RA滑膜组织成纤维细胞产生趋化因子的影响。RA患者的滑膜组织外植体分泌的趋化因子IL-8和生长相关基因产物α(GROAlpha)在SASP的典型临床剂量为2g/d的大范围浓度范围内减少。SP能显著降低RA滑膜组织外植体分泌IL-8(22%)、GROα(55%)和单核细胞趋化蛋白-1(MCP-1)(42%)(P<；0.05)。5ASA对RA滑膜组织外植体产生IL-8和MCP-1无影响，但增加GROα的产生。在IL-1β刺激的RA滑膜组织成纤维细胞中，SASP显著增加趋化因子的分泌，而SP显著降低IL-8(24%)和GROα(21%)的分泌(P<；0.05)。流式细胞仪检测显示，SP处理后RA滑膜组织中表达IL-8的成纤维细胞数量无明显变化。这些数据表明，SASP可能通过其代谢产物SP减少炎性趋化因子IL-8、GROα和MCP-1的分泌来减轻RA的炎症。
Rheumatoid arthritis (RA) is an aggressive inflammatory disease in which chemokines are thought to recruit leukocytes and induce angiogenesis. The aim of this study was to investigate the effects of sulfasalazine (SASP) and its metabolites, sulfapyridine (SP), and 5-aminosalicylic acid (5ASA) on chemokine production by RA synovial tissue explants and interleukin (IL)-1beta-stimulated RA synovial tissue fibroblasts using enzyme-linked immunosorbent assays and flow cytometry. Synovial tissue explants from RA patients secreted a decreased amount of the chemokines IL-8 and growth-related gene product alpha (GROalpha) when treated with SASP over a broad range of concentrations based on the typical clinical dosage of 2 g/day. SP had a significant effect in that it decreased RA synovial tissue explant secretion of IL-8 (22%), GROalpha (55%), and monocyte chemotactic protein-1 (MCP-1) (42%) (P < 0.05). 5ASA had no effect on RA synovial tissue explant production of IL-8 and MCP-1, while increasing GROalpha production. In IL-1beta-stimulated RA synovial tissue fibroblasts, SASP significantly increased chemokine secretion, while SP significantly decreased IL-8 (24%) and GROalpha (21%) secretion (P < 0.05). Flow cytometry showed that the number of IL-8 expressing RA synovial tissue fibroblasts did not significantly change following SP treatment. These data suggest that SASP may function to reduce inflammation in RA through the effects of its metabolite SP to reduce the secretion of the inflammatory chemokines IL-8, GROalpha, and MCP-1.