Fania Luca, Zampetti Anna, Guerriero Giuseppe, Feliciani Claudio
Department of Dermatology, Policlinico A. Gemelli, Università Cattolica del Sacro Cuore, Roma, Italy.
Antiinflamm Antiallergy Agents Med Chem. 2012;11(3):238-42. doi: 10.2174/1871523011202030238.
Human epidermis shows a non-neuronal cholinergic system including keratinocyte (kc) acetylcholine (Ach) axis which is composed by enzymes and two families of Ach receptors (muscarinic and nicotinic receptors). The activity of these two receptors can regulate the interkeratinocytes and kcs-extracellular matrix adhesion modifying the regulation of intercellular adhesion molecules like cadherins and integrins. Some authors demonstrate that acantholysis in pemphigus depends not only on anti desmogleins antibodies (abs) (mostly IgG) but even on other abs directed against kc membrane antigens (e.g. anti Ach receptors Abs). In the early phase of pemphigus pathogenesis, anti Ach receptors Abs block Ach signaling essential for cell shape and intercellular adhesion and increase the phosphorylation of adhesion molecules. Combined with the action of abs antidesmogleins, anti Ach receptors Abs cause the acantholytic phenomenon. In vitro experiments show that high doses of Ach in acantholytic kcs can rapidly reverse this pathologic event. In vivo experiments using neonatal mice model of Pemphigus have demonstrated that cholinergic agonists reduce these lesions. Therapy with pyridostigmine bromide and Nicotinamide per os or pilocarpine used topically, drugs that present cholinomimetic effects, has lead to encouraging results in patients affected by Pemphigus disease. Cholinergic agents could have a strategic role in the therapy of pemphigus since they could be responsible for the early stage of acantholytic diseases.
人类表皮显示出一个非神经元胆碱能系统，包括角质形成细胞（KC）乙酰胆碱（Ach）轴，该轴由酶和两类Ach受体（毒蕈碱型和烟碱型受体）组成。这两类受体的活性可调节角质形成细胞间以及KC与细胞外基质的黏附，从而改变钙黏蛋白和整合素等细胞间黏附分子的调节。一些作者表明，天疱疮中的棘层松解不仅取决于抗桥粒芯糖蛋白抗体（主要是IgG），还取决于其他针对KC膜抗原的抗体（例如抗Ach受体抗体）。在天疱疮发病机制的早期阶段，抗Ach受体抗体阻断了对细胞形态和细胞间黏附至关重要的Ach信号传导，并增加了黏附分子的磷酸化。与抗桥粒芯糖蛋白抗体的作用相结合，抗Ach受体抗体导致棘层松解现象。体外实验表明，在发生棘层松解的KC中高剂量的Ach可迅速逆转这一病理事件。使用天疱疮新生小鼠模型的体内实验表明，胆碱能激动剂可减轻这些病变。口服溴吡斯的明和烟酰胺或局部使用毛果芸香碱进行治疗，这些具有拟胆碱作用的药物，已在天疱疮患者中取得了令人鼓舞的结果。胆碱能药物可能在天疱疮治疗中具有重要作用，因为它们可能与棘层松解性疾病的早期阶段有关。
