RESUMO
We have previously identified the filaggrin (FLG)-like protein, hornerin (HRNR). Recently, there have been several reports regarding the relationship between HRNR and atopic dermatitis (AD). In the present study, we examined HRNR expression in the skin lesions of seven unrelated patients with AD to clarify the role of HRNR in the pathogenesis of AD. HRNR was detected in chronic AD lesions (n = 4), whereas no HRNR signals were observed in acute AD lesions (n = 3). HRNR was detected in the cytokeratin 6-expressing epidermis, and Ki67-positive keratinocytes were more abundant in the HRNR-positive epidermis. These findings suggest that HRNR may be associated with epidermal hyperproliferation in AD lesions. Next, we examined HRNR expression in skin diseases associated with hyperkeratosis. HRNR signals were irregularly observed in different cells from those expressing FLG in epidermolytic ichthyosis and actinic keratosis. Therefore, HRNR may play a unique role in the molecular process of cornification.
Assuntos
Dermatite Atópica , Dermatopatias , Humanos , Proteínas de Ligação ao Cálcio/metabolismo , Dermatite Atópica/patologia , Epiderme/patologia , Proteínas de Filamentos Intermediários/metabolismo , Queratinócitos/metabolismo , Pele/patologia , Dermatopatias/metabolismoAssuntos
Melanoma , Púrpura Trombocitopênica Idiopática , Neoplasias Uveais , Humanos , Púrpura Trombocitopênica Idiopática/induzido quimicamente , Púrpura Trombocitopênica Idiopática/tratamento farmacológico , Inibidores de Checkpoint Imunológico/efeitos adversos , Melanoma/tratamento farmacológico , Melanoma/patologia , Neoplasias Uveais/tratamento farmacológicoRESUMO
Atopic dermatitis (AD) is a chronic inflammatory skin disorder with elevated interleukin (IL)-4 and IL-13 signatures and extensive barrier dysfunction, which is correlated with the downregulation of filaggrin (FLG). FLG is a member of the S100 fused-type protein family and this family also includes cornulin (CRNN), filaggrin-2 (FLG2), hornerin (HRNR) repetin (RPTN), trichohyalin (TCHH) and trichohyalin-like 1 (TCHHL1). The present study aimed to examine the effects of IL-4 and IL-13 and the downregulation of FLG on the expression of S100 fused-type proteins using a three-dimensional (3D) AD skin model by immunohistochemical study and quantitative polymerase chain reaction. In the 3D AD skin model, which was generated by a stimulation of recombinant IL-4 and IL-13, the expression of FLG, FLG2, HRNR and TCHH was decreased, while that of RPTN was increased in comparison to the 3D control skin. In the FLG knockdown (KD) 3D skin model, which was generated using FLG siRNA, the expression of HRNR was increased. The expression of the other proteins did not differ to a statistically significant extent. The expression of fused-S100 type protein family members may differ in AD skin. This suggests that these proteins play different roles in the pathogenesis of AD.
Assuntos
Dermatite Atópica , Humanos , Dermatite Atópica/metabolismo , Proteínas Filagrinas , Interleucina-4/metabolismo , Interleucina-13/metabolismo , Pele/metabolismo , Proteínas S100/genética , Proteínas S100/metabolismo , Proteínas de Filamentos Intermediários/genética , Proteínas de Filamentos Intermediários/metabolismoRESUMO
Hailey-Hailey disease (HHD) is an autosomal dominant genetic disease caused by a mutation of the ATP2C1 gene. Corticosteroids, antibiotics or cyclosporine have been administered to reduce inflammation and prevent flare-ups, but the efficacy is not always sufficient. We herein report two cases of HHD effectively treated with apremilast and review the previous literature. Patient 1 was a 28-year-old male and patient 2 was a 35-year-old female. Both patients were diagnosed with HHD based on histological and genetic analyses. Both patients were treated with oral antibiotics or topical corticosteroids, but their symptoms were refractory, therefore apremilast was administered to both patients. Two weeks later, the skin lesion of both patients was improved. No adverse reaction was observed except for mild headache in patient 2. There have been 13 reported cases of HHD treated with apremilast, including our cases. Eight cases showed a good response to apremilast, whereas five cases showed no response. There seems to be no association between the disease severity and efficacy of apremilast, although the reason remains unknown. Interestingly, an early improvement of the HHD lesion was observed in all good response cases. Although digestive symptoms, headache, and myalgia were observed as adverse events, the treatment was well-tolerated. The accumulation of a greater number of similar cases and further research will be required. We hypothesize that apremilast may be a useful therapeutic option for skin lesions of HHD.