Adenovirus-mediated gene transfer of adiponectin reduces the severity of collagen-induced arthritis in mice
Adenovirus-mediated gene transfer of adiponectin reduces the severity of collagen-induced arthritis in mice
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DOI：
10.1016/j.bbrc.2008.11.005
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发表时间：
2009-01-09
影响因子：
3.1
通讯作者：
Shimomura, Iichiro
中科院分区：
文献类型：
--
作者：
Ebina, Kosuke;Shima, Kazuya;Shimomura, Iichiro
脂联素(APN)是一种由脂肪组织释放的具有抗炎作用的激素。本研究旨在观察APN全身给药对小鼠关节炎模型的治疗作用。用雄性DBA1/J小鼠诱导胶原诱导性关节炎(CIA)，在关节炎进展前或进展过程中分别注射编码人APN的腺病毒载体(Ad-APN)或β-半乳糖苷酶(Ad-β-Gal)作为对照。在两个时间点全身性应用APN均可显著降低CIA的临床疾病活动评分。此外，关节炎进展前的APN治疗显著降低了炎症和软骨损伤、骨侵蚀的组织学评分，以及关节中促炎症细胞因子的mRNA水平，而不改变固定的抗胶原抗体水平。免疫组织化学染色显示，Ad-APN感染CIA小鼠关节内补体C1q和C3沉积受到明显抑制。这些结果为全身注射APN预防炎症和关节破坏提供了新的证据。(C)2008 Elsevier Inc.保留所有权利。
Adiponectin (APN) is a hormone released by adipose tissue with anti-inflammatory properties. The purpose Of this study was to examine the therapeutic effects of systemic delivery of APN in murine arthritis model. Collagen-induced arthritis (CIA) was induced in male DBA1/J mice, and adenoviral vectors encoding human APN (Ad-APN) or beta-galactosidase (Ad-beta-gal) as control were injected either before or during arthritis progression. Systemic APN delivery at both time points significantly decreased clinical disease activity scores of CIA. In addition, APN treatment before arthritis progression significantly decreased histological scores of inflammation and cartilage damage, bone erosion, and mRNA levels of pro-inflammatory cytokines in the joints, without altering set-Urn anti-collagen antibodies levels. Immunohistochemical staining showed significant inhibition of complement C1q and C3 deposition in the joints of Ad-APN infected CIA mice. These results provide novel evidence that systemic APN delivery prevents inflammation and joint destruction ill murine arthritis model. (C) 2008 Elsevier Inc. All rights reserved.