Role of PKC and ERK Signaling in Epidermal Blistering and Desmosome Regulation in Pemphigus

Desmosomes reinforce cohesion of epithelial cells at the interface between adjacent cells. They include the cadherin-type adhesion molecules desmoglein 1 (Dsg1) and Dsg3. Pemphigus vulgaris (PV) is an autoimmune disease in which circulating autoantibodies (PV-IgG) targeting Dsg1 and 3 cause characteristic epidermal blister formation. It has been shown that PV-IgG binding induced activation of kinases such as ERK and PKC, and inhibition of these signaling pathways prevented loss of cell cohesion in cell cultures. However, the role of Erk and PKC in blister formation and regulation of desmosome ultrastructure in human skin are unknown. Accordingly, we assessed the role of PKC and ERK signaling pathways in blister formation and regulation of desmosome ultrastructure in human epidermis. Here we performed electron microscopy analyses using human skin explants injected with PV-IgG together with inhibitors for PKC or ERK signaling. Inhibition of PKC was not effective to prevent suprabasal blister formation or ultrastructural alterations of desmosomes. In contrast, inhibition of ERK signaling significantly ameliorated blister formation and decrease in the number of desmosomes whereas shortening and splitting of desmosomes and keratin filament insertion were not different from samples treated with PV-IgG alone. However, apical desmosomes between basal and suprabasal cells remained unaltered when ERK signaling was inhibited. Therefore, our results show that inhibition of ERK but not PK...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research

Related Links:

Pemphigus is an autoimmune bullous disease characterized by IgG production against desmogleins. The major sites of autoantibody production are thought to be lymph nodes, spleen, and bone marrow. Previously, it has been suggested that autoreactive B cells might exist in the skin lesions in pemphigus and produce autoantibodies. In their report, Zhou et  al. expanded their previous studies and reported that ectopic lymphoid-like structures were found in pemphigus skin lesions, wherein B-cell differentiation and lesional B-cell expansion might progress.
Source: Journal of Investigative Dermatology - Category: Dermatology Authors: Tags: Commentary Source Type: research
Pemphigus is a chronic autoimmune blistering disorder, characterized by (muco-)cutaneous erosions due to autoantibodies against desmoglein 3 and/or 1. Pemphigus induction might be associated with drugs, malignancy or radiation therapy (RT); the latter being only rarely described. A rigorous literature review revealed around 30 cases of RT-associated pemphigus, which had been primarily treated with topical and/or systemic steroids, in some cases also dapsone or few other immunosuppressive agents were given. The most common underlying cancer type was breast cancer. We here present a 63-year-old male patient, who was pre-trea...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
Publication date: Available online 18 January 2020Source: Gynecologic Oncology ReportsAuthor(s): Bijan Morshedi, Kari RingAbstractPemphigus is a group of autoimmune intraepidermal blistering diseases caused by immunoglobulins directed against keratinocyte cell surface components. In this case report, we identify a non-classical paraneoplastic pemphigus (PNP) foliaceous related to an undifferentiated uterine sarcoma.The patient is a 54-year-old female with a past medical history of arthritis who presented with worsening fatigue in November 2017 and an itchy, blistering, erythematous annular plaque that first appeared on her...
Source: Gynecologic Oncology Reports - Category: OBGYN Source Type: research
Authors: Pires CAA, Einecke YS, Pereira NG, Costa CCC, Cunha ACDS, Moreira AG, Rodrigues FDN, Xavier MB Abstract Background: Pemphigus are rare chronic autoimmune blistering disorders with challenging therapeutic management.Objective: To investigate the therapeutic outcomes of pemphigus patients admitted to a dermatology referral service in northern Brazil.Materials and methods: We conducted a retrospective analysis of 32 patients with histopathological diagnosis of pemphigus between 2010 and 2016. Clinical and epidemiological data were collected. Therapeutic outcome was evaluated according to the criteria proposed...
Source: Journal of Dermatological Treatment - Category: Dermatology Tags: J Dermatolog Treat Source Type: research
CONCLUSIONS AND CLINICAL IMPORTANCE: BTKi monotherapy may have beneficial effects in some cases of cPF. PMID: 31899567 [PubMed - as supplied by publisher]
Source: Veterinary Dermatology - Category: Veterinary Research Authors: Tags: Vet Dermatol Source Type: research
Authors: Shahidi-Dadras M, Pishgahi M, Tabary M, Kheradmand Z, Araghi F, Dadkhahfar S, Robati RM Abstract Background: Pemphigus vulgaris which is an autoimmune dermatological disorder characterized by vesiculobullous lesions over the skin and mucosae may also give rise to cardiac disease. Global Longitudinal Strain (GLS) measurement may help to predict cardiac dysfunction in these patients.Method: In this prospective study, the global longitudinal strain was measured before and after steroid pulse therapy in pemphigus vulgaris patients using 2D speckle-tracking echocardiography. Moreover, blood pressure, pulse rate...
Source: Journal of Dermatological Treatment - Category: Dermatology Tags: J Dermatolog Treat Source Type: research
We report the case of a 13-year-old girl suffering from Crohn's disease (CD) and primary sclerosing cholangitis (PSC) who developed PV after application of a tissue expander for surgical removal of a giant congenital melanocytic nevus (GCMN). To the best of our knowledge, the case presented here is the first report of PV possibly associated with the application of a tissue expander and also the first report of coexistence of PV with either PSC or with PSC and CD in the same patient. Triggering or acute exacerbation of PV may be considered a possible side-effect of tissue expander application, especially in patients with a ...
Source: Acta Dermatovenerologica Alpina, Panonica, et Adriatica - Category: Dermatology Tags: Acta Dermatovenerol Alp Pannonica Adriat Source Type: research
ConclusionWhile corticosteroid in combination with either AZA or MMF is an effective therapeutic regimen for the treatment of pemphigus, MMF demonstrates a shorter time to achieve CR on therapy and has a significantly higher steroid-sparing effect.
Source: Dermatology and Therapy - Category: Dermatology Source Type: research
ConclusionsAdjunctive procedures that can facilitate a decrease in the cumulative dosages of corticosteroids and immunosuppressants have great value in the management of PV. CO2 laser vaporization is a safe procedure with minimal morbidity and no long-term side effects and should be considered as an adjunctive treatment option for management of recalcitrant lesions in patients with oral PV.
Source: Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology - Category: ENT & OMF Source Type: research
We present a case of a 50-year-old man with an unremarkable past medical history who smokes 20 cigarettes every day. For the last 3 months, he has complained of pain on the gums. Clinical examination showed multiple white plaques on the buccal gingiva of all 4 quadrants, with a verrucous appearance, some of which had a reddish area. Incisional biopsies were performed of the lesions from the gingiva with clinical diagnosis of proliferative multifocal leukoplakia as well as a microbiologic culture intake.
Source: Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontics - Category: ENT & OMF Authors: Source Type: research
More News: Allergy & Immunology | Autoimmune Disease | Pemphigus | Skin