Akbarzadeh Reza, Yu Xinhua, Vogl Thomas, Ludwig Ralf J, Schmidt Enno, Zillikens Detlef, Petersen Frank
Priority Area Asthma & Allergy, Research Center Borstel, 23845 Borstel, Germany; Airway Research Center North (ARCN), Members of the German Center for Lung Research (DZL), Germany; Lübeck Institute of Experimental Dermatology (LIED), University of Lübeck, Germany.
Priority Area Asthma & Allergy, Research Center Borstel, 23845 Borstel, Germany; Airway Research Center North (ARCN), Members of the German Center for Lung Research (DZL), Germany; Laboratory of Autoimmunity, The Medical College of Xiamen University, Xiamen University, 361005 Xiamen, China.
J Dermatol Sci. 2016 Mar;81(3):165-72. doi: 10.1016/j.jdermsci.2015.12.001. Epub 2015 Dec 2.
Myeloid-related protein-8 (MRP-8) and its heterodimeric partner, MRP-14 belong to the group of danger-associated molecular patterns (DAMPs) and are associated with numerous chronic human disorders. However, their functional role in autoimmunity remains largely unclear.
Here, we examined the involvement of MRP-8/-14 in two difficult-to-treat autoimmune blistering diseases, epidermolysis bullosa acquisita (EBA) and bullous pemphigoid (BP).
MRP-8/-14 concentrations in the sera of EBA and BP patients were quantified by ELISA. Experimental EBA and BP in mice were induced by transfer of antibodies directed against type VII or XVII collagen, respectively. Expression of MRP-8/-14 was analyzed in skin samples of these experimental mouse models. The functional role of MRP-8/-14 proteins was evaluated by the induction of experimental EBA and BP in MRP-14-deficient mice.
We found serum levels of MRP-8/-14 to be elevated in both, EBA and BP patients. Furthermore, in the lesional skin of mice with experimental diseases expression of MRP-8/-14 was increased as compared to healthy controls. However, MRP-14-deficient mice were fully susceptible to experimental disease with a phenotype comparable to that of wild type controls.
Although MRP-8/-14 expression is highly increased in experimental as well as human disease, these proteins do not contribute to the pathogenesis in the effector phase of EBA and BP.
髓样相关蛋白8（MRP-8）及其异源二聚体伴侣MRP-14属于危险相关分子模式（DAMP）组，与多种慢性人类疾病相关。然而，它们在自身免疫中的功能作用仍 largely 不清楚。
在此，我们研究了MRP-8/-14在两种难以治疗的自身免疫性水疱病，获得性大疱性表皮松解症（EBA）和大疱性类天疱疮（BP）中的作用。
通过ELISA定量EBA和BP患者血清中MRP-8/-14的浓度。分别通过转移针对VII型或XVII型胶原的抗体在小鼠中诱导实验性EBA和BP。在这些实验小鼠模型的皮肤样本中分析MRP-8/-14的表达。通过在MRP-14缺陷小鼠中诱导实验性EBA和BP来评估MRP-8/-14蛋白的功能作用。
我们发现EBA和BP患者血清中MRP-8/-14水平均升高。此外，与健康对照相比，患有实验性疾病的小鼠病变皮肤中MRP-8/-14的表达增加。然而，MRP-14缺陷小鼠对实验性疾病完全易感，其表型与野生型对照相当。
尽管MRP-8/-14在实验性和人类疾病中的表达均高度增加，但这些蛋白在EBA和BP的效应阶段对发病机制没有贡献。
