Mavropoulos Athanasios, Orfanidou Timoklia, Liaskos Christos, Smyk Daniel S, Spyrou Vassiliki, Sakkas Lazaros I, Rigopoulou Eirini I, Bogdanos Dimitrios P
Cellular Immunotherapy and Molecular Immunodiagnostics, Institute for Research and Technology-Thessaly (I.RE.TE.TH), 41222 Larissa, Greece ; Institute of Liver Studies, Transplantation Immunology and Mucosal Biology, King's College London School of Medicine at King's College Hospital, Denmark Hill Campus, London SE5 9RS, UK.
Autoimmune Dis. 2013;2013:728529. doi: 10.1155/2013/728529. Epub 2013 Jul 10.
p38 mitogen activated protein kinase (p38 MAPK) signaling plays a major role in the modulation of immune-mediated inflammatory responses and therefore has been linked with several autoimmune diseases. The extent of the involvement of p38 MAPK in the pathogenesis of autoimmune blistering diseases has started to emerge, but whether it pays a critical role is a matter of debate. The activity of p38 MAPK has been studied in great detail during the loss of keratinocyte cell-cell adhesions and the development of pemphigus vulgaris (PV) and pemphigus foliaceus (PF). These diseases are characterised by autoantibodies targeting desmogleins (Dsg). Whether autoantibody-antigen interactions can trigger signaling pathways (such as p38 MAPK) that are tightly linked to the secretion of inflammatory mediators which may perpetuate inflammation and tissue damage in pemphigus remains unclear. Yet, the ability of p38 MAPK inhibitors to block activation of the proapoptotic proteinase caspase-3 suggests that the induction of apoptosis may be a consequence of p38 MAPK activation during acantholysis in PV. This review discusses the current evidence for the role of p38 MAPK in the pathogenesis of pemphigus. We will also present data relating to the targeting of these cascades as a means of therapeutic intervention.
p38丝裂原活化蛋白激酶（p38 MAPK）信号传导在免疫介导的炎症反应调节中起主要作用，因此与多种自身免疫性疾病有关。p38 MAPK在自身免疫性水疱病发病机制中的参与程度已开始显现，但它是否起关键作用仍存在争议。在角质形成细胞细胞间粘附丧失以及寻常型天疱疮（PV）和落叶型天疱疮（PF）发展过程中，对p38 MAPK的活性进行了详细研究。这些疾病的特征是针对桥粒芯糖蛋白（Dsg）的自身抗体。自身抗体 - 抗原相互作用是否能触发与炎症介质分泌紧密相关的信号通路（如p38 MAPK），而这些炎症介质可能使天疱疮中的炎症和组织损伤持续存在，目前尚不清楚。然而，p38 MAPK抑制剂阻断促凋亡蛋白酶半胱天冬酶 - 3激活的能力表明，在PV棘层松解过程中，细胞凋亡的诱导可能是p38 MAPK激活的结果。本综述讨论了p38 MAPK在天疱疮发病机制中作用的当前证据。我们还将展示有关靶向这些级联反应作为治疗干预手段的数据。
