From topical antidote against skin irritants to a novel counter-irritating and anti-inflammatory peptide
From topical antidote against skin irritants to a novel counter-irritating and anti-inflammatory peptide
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DOI：
10.1016/j.taap.2008.01.038
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发表时间：
2008-06-15
影响因子：
3.8
通讯作者：
Wormser, Uri
中科院分区：
文献类型：
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作者：
Brodsky, Berta;Erlanger-Rosengarten, Avigail;Wormser, Uri
本研究的主要目的是研究局部碘对化学和热刺激引起的皮肤损伤的抗刺激活性的机制。通过将豚鼠皮肤暴露在热刺激下，然后进行局部碘处理和皮肤提取，证实了碘通过诱导内源性抗炎因子发挥其活性的假设。将提取物注射到幼稚豚鼠体内后，热引起的刺激减少了 69%。这种保护因子被鉴定为一种新的九肽（组蛋白 H2A 36-44、H-Lys-Gly-Asn-Tyr-Ala-Glu-Arg-Ileu-Ala-OH），可使热暴露豚鼠的刺激评分降低 40%。鼠类类似物（H-Lys-Gly-His-Tyr-Ala-Glu-Arg-ValGly-OH，称为 IIIM1）以剂量依赖性钟形方式减少硫芥 (SM) 诱导的耳肿胀，达到 1 mg/kg 的峰值活性。转染该肽的培养角质形成细胞比对照细胞对 SM 具有更强的抵抗力。该肽以浓度依赖性方式抑制活化中性粒细胞的氧化爆发。此外，该肽以剂量依赖性钟形方式减少葡萄糖氧化酶诱导的小鼠皮肤水肿。除了热和化学引起的皮肤刺激之外，这种新型肽还可能用于治疗牛皮癣和天疱疮等慢性皮肤疾病以及多发性硬化症、关节炎和结肠炎等非皮肤炎症性疾病。 (c) 2008 Elsevier Inc. 保留所有权利。
The primary purpose of the present study was to investigate the mechanism of the counter-irritating activity of topical iodine against skin lesions induced by chemical and thermal stimuli. The hypothesis that iodine exerts its activity by inducing an endogenous anti-inflammatory factor was confirmed by exposing guinea pig skin to heat stimulus followed by topical iodine treatment and skin extraction. Injection of the extract into naive guinea pigs reduced heat-induced irritation by 69%. The protective factor, identified as a new nonapeptide (histone H2A 36-44, H-Lys-Gly-Asn-Tyr-Ala-Glu-Arg-Ileu-Ala-OH), caused reduction of 40% in irritation score in heat-exposed guinea pigs. The murine analog (H-Lys-Gly-His-Tyr-Ala-Glu-Arg-ValGly-OH, termed IIIM1) reduced sulfur mustard (SM)-induced ear swelling at a dose-dependent bell-shape manner reaching peak activity of 1 mg/kg. Cultured keratinocytes transfected with the peptide were more resistant towards SM than the control cells. The peptide suppressed oxidative burst in activated neutrophils in a concentration-dependent manner. In addition, the peptide reduced glucose oxidase-induced skin edema in mice at a dose-dependent bell-shape manner. Apart from thermal and chemical-induced skin irritation this novel peptide might be of potential use in chronic dermal disorders such as psoriasis and pemphigus as well as non-dermal inflammatory diseases like multiple sclerosis, arthritis and colitis. (c) 2008 Elsevier Inc. All rights reserved.