Interleukin 10 attenuates neointimal proliferation and inflammation in aortic allografts by a heme oxygenase-dependent pathway
Interleukin 10 attenuates neointimal proliferation and inflammation in aortic allografts by a heme oxygenase-dependent pathway
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DOI：
10.1073/pnas.0502407102
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发表时间：
2005-05-17
影响因子：
11.1
通讯作者：
Agarwal, A
中科院分区：
文献类型：
--
作者：
Chen, SF;Kapturczak, MH;Agarwal, A
白细胞介素10 （IL-10）是一种多效性细胞因子，具有抗炎、免疫抑制和免疫刺激的特性。以血管新生内膜增生为特征的慢性同种异体移植排斥反应是器官移植损失的主要原因，特别是在心脏和肾脏移植受者中。在主动脉移植的Dark Agouti to Lewis大鼠模型中，我们评估了单次肌肉注射重组腺相关病毒载体（血清型1）编码IL-10 （rAAV1-IL-10）对新内膜增殖和炎症的影响。rAAV1-IL-10治疗导致新生内膜增殖和巨噬细胞、T淋巴细胞和B淋巴细胞的移植物浸润显著减少。IL-10对同种异体主动脉移植物保护作用的机制涉及血红素加氧酶1 (HO-1)，因为HO活性的抑制不仅逆转新生内膜增殖，而且逆转炎症细胞浸润。我们的研究结果表明，IL-10可以减缓新内膜增殖和炎症浸润，并强烈暗示HO-1是IL-10调节慢性血管排斥反应相关炎症反应的重要中介。
Interleukin 10 (IL-10) is a pleiotropic cytokine with well known antiinflammatory, immunosuppressive, and immunostimulatory properties. Chronic allograft rejection, characterized by vascular neointimal proliferation, is a major cause of organ transplant loss, particularly in heart and kidney transplant recipients. In a Dark Agouti to Lewis rat model of aortic transplantation, we evaluated the effects of a single intramuscular injection of a recombinant adeno-associated viral vector (serotype 1) encoding IL-10 (rAAV1-IL-10) on neointimal proliferation and inflammation. rAAV1-IL-10 treatment resulted in a significant reduction of neointimal proliferation and graft infiltration with macrophages and T and B lymphocytes. The mechanism underlying the protective effects of IL-10 in aortic allografts involved heme oxygenase 1 (HO-1) because inhibition of HO activity reversed not only neointimal proliferation but also inflammatory cell infiltration. Our results indicate that IL-10 attenuates neointimal proliferation and inflammatory infiltration and strongly imply that HO-1 is an important intermediary through which IL-10 regulates the inflammatory responses associated with chronic vascular rejection.