IL-1β- and IL-4-induced down-regulation of autotaxin mRNA and PC-1 in fibroblast-like synoviocytes of patients with rheumatoid arthritis (RA)
IL-1β- and IL-4-induced down-regulation of autotaxin mRNA and PC-1 in fibroblast-like synoviocytes of patients with rheumatoid arthritis (RA)
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DOI：
10.1046/j.1365-2249.2001.01432.x
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发表时间：
2001-01-01
影响因子：
4.6
通讯作者：
Langner, J
中科院分区：
文献类型：
--
作者：
Kehlen, A;Lauterbach, R;Langner, J
自分泌运动因子 (ATX) 是一种 125 kD 外核苷酸焦磷酸/磷酸二酯酶，最初是从人黑色素瘤细胞中分离和克隆的，作为肿瘤细胞运动的有效刺激剂。 ATX 与浆细胞膜标记 PC-1 具有 44% 的同一性。最近，我们描述了干扰素-γ 可以降低 RA 患者培养的成纤维样滑膜细胞 (SFC) 中 ATX mRNA 的表达。在这项使用竞争性逆转录酶-聚合酶链反应的研究中，我们发现与非 RA 患者的滑膜细胞相比，RA 患者的 SFC 中 ATX mRNA 表达增加。 RA 患者 SFC 中 ATX mRNA 量中位数（440 pg/杯总 RNA）比非 RA 患者滑膜细胞（80 pg/杯总 RNA）或包皮成纤维细胞（MRHF 细胞，90 pg/杯总 RNA）的表达高出五倍。与 RA 患者 SFC 中 ATX mRNA 表达升高相反，我们没有测量这些细胞中 PC-1 mRNA 量的增加。用细胞因子IL-1β或IL-4处理SFC后，SFC裂解物的ATX mRNA量和5'-核苷酸磷酸二酯酶(PDE)活性均降低。 IL-1β和IL-4诱导SFC中PC-1 mRNA和蛋白表达的下调。在用转化生长因子-β处理的SFC中，PC-1 mRNA和蛋白质的表达增加，而对ATX mRNA表达没有检测到显着影响。用于治疗 RA 的药物，如地塞米松、环孢素、甲氨蝶呤和吲哚美辛，对 ATX mRNA 或 PC-1 mRNA 表达没有显示出统计学上显着的影响。仅己酮可可碱抑制 ATX mRNA 以及 PC-1 mRNA 表达。总之，我们表明在 RA 发炎组织中可检测到的细胞因子对 ATX 和 PC-1 基因表达进行严格调节。进一步的研究将涉及 ATX 蛋白表达的调节以及 ATX 在 RA 中的功能。
Autotaxin (ATX) is a 125-kD ectonucleotide pyrophosphate/phosphodiesterase, which was initially isolated and cloned from human melanoma cells as a potent stimulator of tumour cell motility. ATX shows 44% identity to the plasma cell membrane marker PC-1. Recently, we described the decreased expression of ATX mRNA in cultured fibroblast-like synoviocytes (SFC) of patients with RA by interferon-gamma. In this study using a competitive reverse transcriptase-polymerase chain reaction, we show an increased ATX mRNA expression in SFC from patients with RA in comparison with synoviocytes from non-RA patients. The median ATX mRNA amount in SFC of RA patients (440 pg/mug total RNA) was five-fold higher than the expression in synoviocytes from non-RA patients (80 pg/mug total RNA) or foreskin fibroblasts (MRHF cells, 90 pg/mug total RNA). In contrast to the elevated ATX mRNA expression in SFC of patients with RA, we did not measure increased mRNA amounts of PC-1 in these cells. Both the ATX mRNA amount and the 5'-nucleotide phosphodiesterase (PDE) activity of SFC lysate were reduced after treatment of SFC with the cytokines IL-1 beta or IL-4. IL-1 beta and IL-4 induced a down-regulation of PC-1 mRNA and protein expression in SFC. In SFC treated with transforming growth factor-beta the expression of PC-1 mRNA and protein was increased, whereas no significant effect on ATX mRNA expression was detectable. Pharmacological drugs used in therapy for RA, such as dexamethasone, cyclosporin, methotrexate and indomethacin, did not show a statistically significant effect on either ATX mRNA or PC-1 mRNA expression. Only pentoxifylline suppressed ATX mRNA as well as PC-1 mRNA expression. In conclusion, we show a tight regulation of ATX and PC-1 gene expression by cytokines detectable in the inflamed tissue of RA. Further investigations will deal with the regulation of ATX protein expression as well as with the function of ATX in RA.