Local expression of interleukin-27 ameliorates collagen-induced arthritis.
Local expression of interleukin-27 ameliorates collagen-induced arthritis.
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DOI：
10.1002/art.30324
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发表时间：
2011-08
影响因子：
--
通讯作者：
Shahrara, Shiva
中科院分区：
文献类型：
--
作者：
Pickens, Sarah R.;Chamberlain, Nathan D.;Volin, Michael V.;Mandelin, Arthur M., II;Agrawal, Hemant;Matsui, Masanori;Yoshimoto, Takayuki;Shahrara, Shiva
探讨IL-27对类风湿关节炎（RA）的作用机制。构建了含IL-27转录本的腺病毒，并将其局部递送至胶原诱导关节炎（CIA）小鼠的踝关节。通过测量踝关节周长和组织学分析来评估治疗小鼠与未治疗小鼠的关节炎进展。用ELISA法定量了局部表达腺病毒IL-27的CIA踝关节与对照组相比IL-17及其下游靶点以及促进TH-17细胞分化的细胞因子。两组踝关节均行中性粒细胞和单核细胞迁移免疫染色。最后，通过组织学和测定踝关节血红蛋白水平来定量血管化。我们的研究结果表明，与对照组相比，CIA中IL-27的异位表达改善了炎症、内膜肥大和骨侵蚀。与对照组相比，IL-27治疗组血清和关节IL-17水平显著降低。诱导TH-17细胞分化的两种主要细胞因子和IL-17下游靶分子在被迫表达IL-27的CIA踝关节中显著下调。与异位表达IL-27的小鼠相比，对照小鼠的血管化和单核细胞运输水平更高。我们的研究结果表明，增加IL-27水平可缓解CIA踝关节关节炎。这种关节炎的改善包括降低CIA血清和关节IL-17水平，并导致IL-17介导的单核细胞募集和血管生成减少。因此，IL-27可能是RA的治疗靶点。
To determine the mechanism of action of IL-27 against rheumatoid arthritis (RA). Adenovirus containing IL-27 transcript was constructed and was locally delivered into the ankles of collagen-induced arthritis (CIA) mice. Progression of arthritis was assessed in treated versus untreated mice by measuring ankle circumference and through histological analysis. IL-17 and its downstream targets as well as cytokines promoting TH-17 cell differentiation were quantified by ELISA in CIA ankles locally expressing adenoviral IL-27 versus controls. Ankles from both treatment groups were immunostained for neutrophil and monocyte migration. Last, vascularization was quantified by histology and by determining ankle hemoglobin levels. Our results demonstrate that ectopic expression of IL-27 in CIA ameliorates inflammation, lining hypertrophy, and bone erosion compared to the control group. Serum and joint IL-17 levels were significantly reduced in the IL-27 treatment group compared to controls. Two of the main cytokines which induce TH-17 cell differentiation and IL-17 downstream target molecules were greatly downregulated in CIA ankles receiving forced expression of IL-27. The control mice had higher levels of vascularization and monocyte trafficking compared to those mice ectopically expressing IL-27. Our results suggest that increased IL-27 levels relieve arthritis in CIA ankles. This amelioration of arthritis involves a reduction in CIA serum and joint IL-17 levels and results in decreased IL-17-mediated monocyte recruitment and angiogenesis. Hence, IL-27 may be a therapeutic target in RA.
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影响因子：
30.5
作者：
Manel, Nicolas;Unutmaz, Derya;Littman, Dan R.
通讯作者：
Littman, Dan R.
影响因子：
32.4
作者：
Pflanz, S;Timans, JC;Kastelein, RA
通讯作者：
Kastelein, RA
影响因子：
64.8
作者：
Chen, Q;Ghilardi, N;de Sauvage, FJ
通讯作者：
de Sauvage, FJ
影响因子：
27.4
作者：
Niedbala, W.;Cai, B.;Liew, F. Y.
通讯作者：
Liew, F. Y.
影响因子：
4.4
作者：
Lubberts, E;van den Bersselaar, L;van den Berg, WB
通讯作者：
van den Berg, WB