Novel sulfated polysaccharides disrupt cathelicidins, inhibit RAGE and reduce cutaneous inflammation in a mouse model of rosacea.
Novel sulfated polysaccharides disrupt cathelicidins, inhibit RAGE and reduce cutaneous inflammation in a mouse model of rosacea.
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DOI：
10.1371/journal.pone.0016658
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发表时间：
2011-02-09
期刊：
影响因子：
3.7
通讯作者：
Krueger G
中科院分区：
文献类型：
--
作者：
Zhang J;Xu X;Rao NV;Argyle B;McCoard L;Rusho WJ;Kennedy TP;Prestwich GD;Krueger G
酒渣鼻是一种常见的毁容性皮肤病，主要发生在高加索人身上，其特征是面部中央红斑，伴有毛细血管扩张性血管、丘疹和脓疱，并可导致皮肤增厚，特别是在男性的鼻子上，从而产生鼻赘。酒渣鼻也可以产生干燥，发痒的眼睛与刺激的眼睑，角膜炎和角膜疤痕。酒渣鼻的原因已被提出为过量生产的阳离子cathelicidin肽LL-37。我们测试了一类新的非抗凝剂硫酸化阴离子多糖，半合成糖胺聚糖醚（SAGE）的致病途径的关键要素，导致酒渣鼻。SAGE在ng/ml时具有抗炎作用，包括抑制多形核白细胞（PMN）蛋白酶、P-选择素以及晚期糖基化终产物（AGEs）受体与四种代表性配体的相互作用。SAGE结合LL-37并抑制IL-8的产生诱导的LL-37在培养的人角质形成细胞。当在注射前与LL-37混合时，SAGE防止由LL-37直接皮内注射到小鼠皮肤中产生的红斑和PMN浸润。将1%（w/w）SAGE润肤剂局部应用于覆盖的注射皮肤也减少了红斑和来自皮内LL-37的PMN浸润。以SAGE为例的阴离子多糖提供了作为用于红斑痤疮的新的基于机制的疗法的潜力，并且通过扩展其他LL-37介导的和RAGE配体驱动的皮肤疾病。
Rosacea is a common disfiguring skin disease of primarily Caucasians characterized by central erythema of the face, with telangiectatic blood vessels, papules and pustules, and can produce skin thickening, especially on the nose of men, creating rhinophyma. Rosacea can also produce dry, itchy eyes with irritation of the lids, keratitis and corneal scarring. The cause of rosacea has been proposed as over-production of the cationic cathelicidin peptide LL-37. We tested a new class of non-anticoagulant sulfated anionic polysaccharides, semi-synthetic glycosaminoglycan ethers (SAGEs) on key elements of the pathogenic pathway leading to rosacea. SAGEs were anti-inflammatory at ng/ml, including inhibition of polymorphonuclear leukocyte (PMN) proteases, P-selectin, and interaction of the receptor for advanced glycation end-products (RAGE) with four representative ligands. SAGEs bound LL-37 and inhibited interleukin-8 production induced by LL-37 in cultured human keratinocytes. When mixed with LL-37 before injection, SAGEs prevented the erythema and PMN infiltration produced by direct intradermal injection of LL-37 into mouse skin. Topical application of a 1% (w/w) SAGE emollient to overlying injected skin also reduced erythema and PMN infiltration from intradermal LL-37. Anionic polysaccharides, exemplified by SAGEs, offer potential as novel mechanism-based therapies for rosacea and by extension other LL-37-mediated and RAGE-ligand driven skin diseases.
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HMGB1：内源性危险信号。
影响因子：
5.7
作者：
Klune, John R.;Dhupar, Rajeev;Cardinal, Jon;Billiar, Timothy R.;Tsung, Allan
通讯作者：
Tsung, Allan
影响因子：
3.6
作者：
Meingassner, JG;Aschauer, H;Billich, A
通讯作者：
Billich, A
影响因子：
46.9
作者：
Karande, P;Jain, A;Mitragotri, S
通讯作者：
Mitragotri, S
影响因子：
5.1
作者：
Bralley, Eve E.;Greenspan, Phillip;Hartle, Diane K.
通讯作者：
Hartle, Diane K.
影响因子：
5.8
作者：
Betz, G;Nowbakht, P;Imanidis, G
通讯作者：
Imanidis, G