类风湿关节炎患者滑膜成纤维细胞中多巴胺受体表达增加：多巴胺对白细胞介素-8 和白细胞介素-6 的抑制作用。

Increased expression of dopamine receptors in synovial fibroblasts from patients with rheumatoid arthritis: inhibitory effects of dopamine on interleukin-8 and interleukin-6.

机构信息

University Hospital Regensburg, Regensburg, Germany.

出版信息

Arthritis Rheumatol. 2014 Oct;66(10):2685-93. doi: 10.1002/art.38746.

DOI:10.1002/art.38746

PMID:24965369

Abstract

OBJECTIVE

Observations in both animal models of arthritis and patients with rheumatoid arthritis (RA) suggest a role for dopamine and its receptors in RA. Because synovial fibroblasts (SFs) contribute to inflammation and joint destruction in RA, the aim of this study was to investigate dopaminergic pathways in SFs obtained from patients with RA and, for comparison, in SFs from patients with osteoarthritis (OA) undergoing knee joint replacement surgery.

METHODS

The expression of all dopamine receptors (D1 -D5 ) and dopamine transporter was assessed by immunofluorescence and immunohistochemical staining. The levels of dopamine receptor and tyrosine hydroxylase messenger RNA were measured by real-time polymerase chain reaction. The intracellular content of dopamine, its precursor, and its main metabolites was assayed by high-performance liquid chromatography. The influence of dopamine on proinflammatory interleukin-6 (IL-6) and IL-8, matrix metalloproteinase 3, and tissue inhibitor of metalloproteinases 1 (TIMP-1) and TIMP-2 was studied in SFs.

RESULTS

SFs possess an intrinsic dopaminergic system, including dopamine receptors, dopamine transporter, and tyrosine hydroxylase, and contain dopamine, its precursor, and its main metabolites. SFs from patients with RA, in comparison with those from patients with OA, showed increased expression of dopamine receptors D1 and D5 , and exogenous dopamine strongly inhibited the production of IL-8 in patients with RA.

CONCLUSION

SFs from patients with RA and patients with OA show a dopaminergic phenotype. The expression of D1-like dopamine receptors was higher in RASFs, and this increased expression may lead to antiinflammatory effects, as demonstrated by the expression of IL-8. Studies in animal models and patients with RA are needed to assess the therapeutic potential of endogenous, local production of dopamine in synoviocytes.

摘要

目的

关节炎动物模型和类风湿关节炎（RA）患者的观察结果表明，多巴胺及其受体在 RA 中起作用。由于滑膜成纤维细胞（SFs）有助于 RA 中的炎症和关节破坏，因此本研究旨在研究从 RA 患者中获得的 SFs 中的多巴胺能途径，并与接受膝关节置换手术的骨关节炎（OA）患者的 SFs 进行比较。

方法

通过免疫荧光和免疫组织化学染色评估所有多巴胺受体（D1-D5）和多巴胺转运体的表达。通过实时聚合酶链反应测量多巴胺受体和酪氨酸羟化酶信使 RNA 的水平。通过高效液相色谱法测定多巴胺、其前体及其主要代谢物的细胞内含量。研究多巴胺对促炎性白细胞介素-6（IL-6）和 IL-8、基质金属蛋白酶 3 以及金属蛋白酶 1（TIMP-1）和 TIMP-2 的影响在 SFs 中。