Department of Pathophysiology and Immunology, Institute of Rheumatology, Warsaw, Poland.
Ann Rheum Dis. 2012 Feb;71(2):262-7. doi: 10.1136/annrheumdis-2011-200123. Epub 2011 Oct 11.
(1) To compare spontaneous and stimuli-induced adipocytokine secretion by articular adipose tissue (AAT) and synovial membrane (SM) explants obtained from patients with rheumatoid arthritis (RA). (2) To investigate the biological activity of AAT and SM released factors.
Tissues were obtained from patients undergoing joint replacement surgery. Tissue explants were treated with proinflammatory cytokines relevant to RA pathogenesis (interleukin 1β (IL-1β), tumour necrosis factor (TNF), interferon γ, IL-15, IL-17, IL-23). Selected adipocytokine (TNF, IL-6, IL-8, IL-1β, IL-1Ra, adiponectin, leptin) concentrations were measured in culture supernatants using ELISA. The biological activity of tissue-conditioned media was evaluated by measuring production of selected factors (IL-6, IL-8, Dickkopf-1, osteoprotegerin) by fibroblast-like synoviocytes (FLS).
Spontaneous cytokine release from AAT was ≤12% of that produced by SM, while leptin was secreted in similar amounts. AAT was highly reactive to proinflammatory cytokines (IL-1β>TNF). AAT treated with IL-1β released four times more leptin, similar amounts of IL-6 and IL-8 and about 20% of TNF, as compared with SM. Upon activation, the IL-1 receptor antagonist (IL-1Ra)/IL-1β ratio was higher in AAT than in SM cultures. Irrespective of activation status, SM produced twice as much adiponectin as AAT. Conditioned media from AAT and SM cultures similarly upregulated IL-6, IL-8, Dickkopf-1 and osteoprotegerin production by rheumatoid FLS.
Rheumatoid AAT is highly reactive tissue which upon stimulation secretes considerable amounts of proinflammatory (IL-6, IL-8, TNF) and anti-inflammatory (IL-1Ra) cytokines and classical adipokines. This tissue releases biologically active factors that intensify pathogenic activities of rheumatoid FLS. Thus, AAT should be considered an important contributor to the pathological processes taking place in the RA joint.
（1）比较来自类风湿关节炎（RA）患者的关节脂肪组织（AAT）和滑膜（SM）组织块的自发性和刺激诱导性脂肪细胞因子分泌。（2）研究 AAT 和 SM 释放因子的生物学活性。
从接受关节置换手术的患者中获取组织。用与 RA 发病机制相关的促炎细胞因子（白细胞介素 1β（IL-1β）、肿瘤坏死因子（TNF）、干扰素 γ、IL-15、IL-17、IL-23）处理组织块。使用 ELISA 测量培养上清液中选定的脂肪细胞因子（TNF、IL-6、IL-8、IL-1β、IL-1Ra、脂联素、瘦素）浓度。通过测量成纤维样滑膜细胞（FLS）产生的选定因子（IL-6、IL-8、Dickkopf-1、骨保护素）来评估组织条件培养基的生物学活性。
AAT 的自发性细胞因子释放量≤SM 产生量的 12%，而瘦素的分泌量则相似。AAT 对促炎细胞因子（IL-1β>TNF）高度反应。与 SM 相比，用 IL-1β 处理的 AAT 释放的瘦素增加了四倍，IL-6 和 IL-8 的量相似，TNF 约为 20%。在激活后，AAT 培养物中的白细胞介素 1 受体拮抗剂（IL-1Ra）/IL-1β 比值高于 SM 培养物。无论激活状态如何，SM 产生的脂联素是 AAT 的两倍。来自 AAT 和 SM 培养物的条件培养基同样上调了类风湿 FLS 中 IL-6、IL-8、Dickkopf-1 和骨保护素的产生。
类风湿 AAT 是一种高度反应性组织，在受到刺激后会分泌大量促炎（IL-6、IL-8、TNF）和抗炎（IL-1Ra）细胞因子和经典脂肪细胞因子。这种组织释放具有生物活性的因子，可增强类风湿 FLS 的致病活性。因此，AAT 应被视为发生在 RA 关节中的病理过程的重要贡献者。
