Immunosuppressive activity of a novel peptide analog of alpha-melanocyte stimulating hormone (α-MSH) in experimental autoimmune uveitis
Immunosuppressive activity of a novel peptide analog of alpha-melanocyte stimulating hormone (α-MSH) in experimental autoimmune uveitis
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DOI：
10.1016/j.jneuroim.2011.04.015
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发表时间：
2011-07-01
影响因子：
3.3
通讯作者：
Perricone, Michael A.
中科院分区：
文献类型：
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作者：
Edling, Andrea E.;Gomes, Danilo;Perricone, Michael A.
自身免疫性葡萄膜炎是一种炎症性疾病的眼睛，可导致疼痛和视力丧失。类固醇和免疫抑制药物是目前唯一的治疗葡萄膜炎的药物，并具有严重的眼部和全身毒性。因此，需要更安全的替代疗法。α-黑素细胞刺激激素（α-MSH）是抑制效应T细胞功能、诱导调节性T细胞并且在某些自身免疫和移植模型中具有有益作用的神经肽。产生了天然α-MSH（dRI-α-MSH）的新型D-氨基酸肽类似物，其被保护免于蛋白酶消化并且对黑皮质素-1受体具有增加的选择性。在实验性自身免疫性葡萄膜炎（EAU）模型中，dRI-α-MSH类似物的全身递送显著抑制疾病进展并保留视网膜结构。眶周注射局部给药同样有效。重要的是，用新的dRI-α-MSH类似物治疗抑制葡萄膜炎，其程度与皮质类固醇地塞米松相似。数据表明，新的dRI-α-MSH类似物显示出抗炎活性，并在葡萄膜炎和其他自身免疫性疾病中具有潜在的治疗用途。(C)2011 Elsevier B. V.保留所有权利。
Autoimmune uveitis is an inflammatory disorder of the eye that can lead to pain and vision loss. Steroids and immunosuppressive drugs are currently the only therapeutics for uveitis and have serious ocular and systemic toxicities. Therefore, safer alternative therapeutics are desired. Alpha-melanocyte stimulating hormone (alpha-MSH) is a neuropeptide that suppresses effector T cell functions, induces regulatory T cells and has beneficial effects in certain autoimmune and transplant models. A novel D-amino acid peptide analog of native alpha-MSH (dRI-alpha-MSH) was produced that was protected from protease digestion and had increased selectivity for the melanocortin-1 receptor. Systemic delivery of the dRI-alpha-MSH analog dramatically suppressed disease progression and retained retinal architecture in the experimental autoimmune uveitis (EAU) model. Local delivery by periorbital injection was equally effective. Importantly, treatment with the novel dRI-alpha-MSH analog suppressed uveitis with a similar magnitude to the corticosteroid, dexamethasone. Data indicate that the novel dRI-alpha-MSH analogs show anti-inflammatory activities and have potential therapeutic use in uveitis and other autoimmune diseases. (C) 2011 Elsevier B.V. All rights reserved.