RESUMO
IL-22 induces STAT3 phosphorylation and mediates psoriasis-related gene expression. However, the signaling mechanism leading from pSTAT3 to the expression of these genes remains unclear. We focused on Bcl-3, which is induced by STAT3 activation and mediates gene expression. In cultured human epidermal keratinocytes, IL-22 increased Bcl-3, which was translocated to the nucleus with p50 via STAT3 activation. The increases in CXCL8, S100As and human ß-defensin 2 mRNA expression caused by IL-22 were abolished by siRNA against Bcl-3. Although CCL20 expression was also augmented by IL-22, the knockdown of Bcl-3 increased its level. Moreover, the combination of IL-22 and IL-17A enhanced Bcl-3 production, IL-22-induced gene expression, and the expression of other psoriasis-related genes, including those encoding IL-17C, IL-19, and IL-36γ. The expression of these genes (except for CCL20) was also suppressed by the knockdown of Bcl-3. Bcl-3 overexpression induced CXCL8 and HBD2 expression but not S100As expression. We also compared Bcl-3 expression between psoriatic skin lesions and normal skin. Immunostaining revealed strong signals for Bcl-3 and p50 in the nucleus of epidermal keratinocytes from psoriatic skin. The IL-22-STAT3-Bcl-3 pathway may be important in the pathogenesis of psoriasis.
Assuntos
Regulação da Expressão Gênica/genética , Interleucinas/metabolismo , Proteínas Proto-Oncogênicas/genética , Psoríase/patologia , Fator de Transcrição STAT3/metabolismo , Pele/patologia , Fatores de Transcrição/genética , Transporte Ativo do Núcleo Celular/fisiologia , Proteína 3 do Linfoma de Células B , Células Cultivadas , Quimiocina CCL20/biossíntese , Ativação Enzimática , Humanos , Interleucina-1/biossíntese , Interleucina-17/biossíntese , Interleucina-17/metabolismo , Interleucina-8/biossíntese , Interleucina-8/genética , Interleucinas/biossíntese , Queratinócitos/metabolismo , Subunidade p50 de NF-kappa B/metabolismo , Fosforilação , Proteínas Proto-Oncogênicas/biossíntese , Psoríase/genética , Interferência de RNA , RNA Mensageiro/biossíntese , RNA Mensageiro/genética , RNA Interferente Pequeno/genética , Proteínas S100/genética , Fatores de Transcrição/biossíntese , beta-Defensinas/biossíntese , beta-Defensinas/genética , Interleucina 22Assuntos
Erupções Acneiformes/induzido quimicamente , Antineoplásicos/efeitos adversos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Receptores ErbB/antagonistas & inibidores , Neoplasias Pulmonares/tratamento farmacológico , Úlcera por Pressão/induzido quimicamente , Quinazolinas/efeitos adversos , Erupções Acneiformes/terapia , Idoso , Feminino , Gefitinibe , Humanos , Japão , Masculino , Recidiva Local de Neoplasia/tratamento farmacológico , Úlcera por Pressão/terapia , Quinazolinas/uso terapêutico , CicatrizaçãoRESUMO
We report a case of pyoderma gangrenosum (PG) associated with nasal septal perforation, pharyngeal ulcers and IgA paraproteinemia. A 28-year-old woman first developed painful undermined ulcers on her perianal, inguinal and axillary areas when she was 22 years old. Histological findings from the cutaneous ulcers showed dermal and epidermal infiltrate of neutrophils, which was compatible with PG. Laboratory examinations did not detect any associations of systemic diseases other than polyclonal IgA paraproteinemia. Nasal fiberscopy revealed septal perforation and multiple ulcers on her pharynx. The biopsy specimen from the pharyngeal ulcers showed a polymorphous cellular infiltrate without necrotizing vasculitis or granuloma. However, there were no atypical lymphocytes that are typically seen in nasal NK/T lymphoma. By immunohistochemical analysis, the infiltrated lymphocytes were proved to be T cells and Epstein-Barr virus encoded RNA (EBER) was not detected. No pulmonary or renal lesions resembling Wegener's granulomatosis were found. Taken together, the nasal septal perforation was considered as nasal involvement of PG.
Assuntos
Granulomatose com Poliangiite/patologia , Septo Nasal/patologia , Faringite/patologia , Pioderma Gangrenoso/diagnóstico , Úlcera/patologia , Adulto , Biópsia por Agulha , Terapia Combinada , Endoscopia/métodos , Feminino , Seguimentos , Granulomatose com Poliangiite/complicações , Granulomatose com Poliangiite/terapia , Humanos , Imunoglobulina A/análise , Imuno-Histoquímica , Japão , Doenças Nasais/complicações , Doenças Nasais/diagnóstico , Doenças Nasais/terapia , Orofaringe/patologia , Faringite/complicações , Faringite/terapia , Pioderma Gangrenoso/complicações , Pioderma Gangrenoso/terapia , Medição de Risco , Índice de Gravidade de Doença , Úlcera/complicações , Úlcera/terapiaRESUMO
AIM: Vascular aging is known to be a major determinant of life expectancy. Recently, perceived age was reported to be a better predictor for mortality than chronological age. Based on these findings, we investigated whether or not perceived age was related to atherosclerosis in a general population. METHODS: The participants were 273 individuals aged ≥ 50 years who participated in the Skin-doc in Anti-Aging Doc program. Facial photos were taken under a shadowless lamp from three directions (antero-posterior, and 60° right and left oblique projection) using a high-resolution digital camera. Perceived age was assessed either by 19 professional nurses in the geriatric ward or using facial identification program software. Carotid intima-media thickness (IMT), radial augmentation index (AI) and brachial-ankle pulse wave velocity (baPWV) were measured as indices for atherosclerosis. RESULTS: The perceived age difference (expressed as the difference between perceived age and chronological age), when estimated either by nurses or software, was significantly and negatively associated with chronological age. Subjects who were evaluated by nurses to be younger than their chronological age had significantly lower carotid IMT after adjustment for chronological age. Conversely, carotid IMT was an independent and negative determinant of looking young, as perceived by nurses. Similar observations were also made between perceived age using facial identification software and carotid IMT. Radial AI and baPWV were not associated with perceived age. CONCLUSION: These findings show that carotid atherosclerosis is related to perceived age. This association might underlie previous findings showing that perceived age predicts life expectancy.