CD40 engagement on synovial fibroblast up-regulates production of vascular endothelial growth factor
CD40 engagement on synovial fibroblast up-regulates production of vascular endothelial growth factor
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DOI：
10.4049/jimmunol.164.10.5055
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发表时间：
2000-05-15
影响因子：
4.4
通讯作者：
Kim, HY
中科院分区：
文献类型：
--
作者：
Cho, CS;Cho, ML;Kim, HY
我们检测了CD 40结合对类风湿性关节炎滑膜成纤维细胞产生血管内皮生长因子（VEGF）的影响。从类风湿性关节炎患者的滑膜组织中制备成纤维细胞样滑膜细胞（FLS），并在CD 40配体转染的（CD 40 L（+））L细胞存在下培养。通过ELISA测定培养上清液中的VEGF水平。CD 40 L（+）L细胞刺激FLS使VEGF的产生增加了4.1倍。类风湿性关节炎滑液中活化T细胞上的CD 40 L也上调FLS的VEGF产生。吲哚美辛和抗IL-1 β、TNF-α和TGF-β抗体均不影响CD 40 L诱导的VEGF产生。用TNF-α、IL-1 β和TGF-β刺激FLS分别使VEGF的产生增加1.6倍、2.0倍和5.2倍，并显示出对CD 40 L产生VEGF的累加效应。用CD 40 L（+）L细胞膜刺激FLS也可上调VEGF mRNA的表达。地塞米松完全消除CD 40 L诱导的VEGF产生。此外，吡咯烷二硫代氨基甲酸酯部分下调CD 40 L诱导的VEGF产生，表明NF-κ B途径部分参与了导致VEGF产生的CD 40 L信号传导。总的来说，这些结果表明，滑膜成纤维细胞上的CD 40和活化的T淋巴细胞上表达的CD 40 L之间的相互作用可能直接参与类风湿性滑膜炎中的新血管形成，通过增强VEGF的产生。
We tested the impact of CD40 engagement on the production of vascular endothelial growth factor (VEGF) from rheumatoid synovial fibroblasts, Fibroblast-like synovial cells (FLS) were prepared from the synovial tissues of rheumatoid arthritis patients and cultured in the presence of CD40 ligand-transfected (CD40L(+)) L cells. VEGF levels were determined in the culture supernatants by ELISA. Stimulation of FLS by CD40L(+) L cells increased the production of VEGF by 4.1-fold over the constitutive levels of unstimulated FLS, The CD40L on activated T cells from rheumatoid synovial fluid also up-regulated VEGF production from FLS. Neither indomethacin nor Abs to IL-1 beta, TNF-alpha, and TGF-beta did affect CD40L-induced VEGF production. Stimulation of FLS with TNF-alpha, IL-1 beta, and TGF-beta increased VEGF production by 1.6-, 2.0-, and 5.2-fold, respectively, and displayed an additive effect on the production of VEGF by CD40L. VEGF mRNA expression was also up-regulated by the stimulation of FLS with membranes from the CD40L(+) L cells. Dexamethasone completely abrogated CD40L-induced VEGF production. In addition, pyrrolidine dithiocarbamate partially down-regulated CD40L-induced VEGF production, showing that the NF-kappa B pathway was partly involved in the signaling of CD40L leading to VEGF production. Collectively, these results suggest that the interaction between CD40 on synovial fibroblasts and CD40L expressed on activated T lymphocytes may be directly involved in the neovascularization in rheumatoid synovitis by enhancing the production of VEGF.