Green tea extract inhibits chemokine production, but up-regulates chemokine receptor expression, in rheumatoid arthritis synovial fibroblasts and rat adjuvant-induced arthritis
Green tea extract inhibits chemokine production, but up-regulates chemokine receptor expression, in rheumatoid arthritis synovial fibroblasts and rat adjuvant-induced arthritis
复制标题
DOI：
10.1093/rheumatology/kep397
复制
发表时间：
2010-03-01
期刊：
影响因子：
5.5
通讯作者：
Ahmed, Salahuddin
中科院分区：
文献类型：
--
作者：
Marotte, Hubert;Ruth, Jeffrey H.;Ahmed, Salahuddin
Objective.评价绿色茶提取物（GTE）在调节人RA滑膜成纤维细胞和大鼠佐剂诱导的关节炎（AIA）中趋化因子产生和趋化因子受体表达中的功效。从人RA滑膜分离的成纤维细胞用于研究。通过ELISA测量活化后调节的正常T细胞表达和分泌的（RANTES）/CCL 5、单核细胞趋化蛋白（MCP）-1/CCL2、生长调节癌基因（GRO）α/CXCL 1和IL-8/CXCL 8的产生。Western blotting检测蛋白激酶C（PKC）δ和c-Jun N-末端激酶（JNK）的磷酸化水平。通过定量RT-PCR测定趋化因子和趋化因子受体表达。GTE给药在大鼠AIA中的益处被确定。GTE（2.5-40 μ g/ml）抑制IL-1 β诱导的人RA滑膜成纤维细胞MCP-1/CCL 2（10 ng/ml）、RANTES/CCL 5、GRO α/CXCL 1和IL-8/CXCL 8的产生（P < 0.05）。然而，GTE抑制RA滑膜成纤维细胞中MCP-1/CCL 2和GRO α/CXCL 1 mRNA的合成。此外，GTE还抑制IL-1 β诱导的PKC δ磷酸化，PKC δ是介导IL-1 β诱导的趋化因子产生的信号传导途径。有趣的是，GTE预孵育增强了组成型和IL-1 β诱导的CCR 1、CCR 2b、CCR 5、CXCR 1和CXCR 2受体表达。GTE给药（200 mg/kg/天p.o.）适度改善大鼠AIA，伴随着MCP-1/CCL 2和GRO α/CXCL 1水平的降低以及GTE给药大鼠关节中CCR-1、-2、-5和CXCR 1受体表达的增强。趋化因子受体过表达和GTE导致的趋化因子产生减少可能是限制RA整体炎症和关节破坏的一种潜在机制。
Objective. Evaluation of the efficacy of green tea extract (GTE) in regulating chemokine production and chemokine receptor expression in human RA synovial fibroblasts and rat adjuvant-induced arthritis (AIA).Methods. Fibroblasts isolated from human RA synovium were used in the study. Regulated upon activation normal T cell expressed and secreted (RANTES)/CCL5, monocyte chemoattractant protein (MCP)-1/CCL2, growth-regulated oncogene (GRO)alpha/CXCL1 and IL-8/CXCL8 production was measured by ELISA. Western blotting was used to study the phosphorylation of protein kinase C (PKC)delta and c-Jun N-terminal kinases (JNK). Chemokine and chemokine receptor expression was determined by quantitative RT-PCR. The benefit of GTE administration in rat AIA was determined.Results. GTE (2.5-40 mu g/ml) inhibited IL-1 beta-induced MCP-1/CCL2 (10 ng/ml), RANTES/CCL5, GRO alpha/CXCL1 and IL-8/CXCL8 production in human RA synovial fibroblasts (P < 0.05). However, GTE inhibited MCP-1/CCL2 and GRO alpha/CXCL1 mRNA synthesis in RA synovial fibroblasts. Furthermore, GTE also inhibited IL-1 beta-induced phosphorylation of PKC delta, the signalling pathway mediating IL-1 beta-induced chemokine production. Interestingly, GTE preincubation enhanced constitutive and IL-1 beta-induced CCR1, CCR2b, CCR5, CXCR1 and CXCR2 receptor expression. GTE administration (200 mg/kg/day p.o.) modestly ameliorated rat AIA, which was accompanied by a decrease in MCP-1/CCL2 and GRO alpha/CXCL1 levels and enhanced CCR-1, -2, -5 and CXCR1 receptor expression in the joints of GTE administered rats.Conclusions. Chemokine receptor overexpression with reduced chemokine production by GTE may be one potential mechanism to limit the overall inflammation and joint destruction in RA.