RESUMO
CCL20 attracts immature dendritic cells and memory T cells and plays a role on mucosal surfaces in inflammation. However, whether Helicobacter pylori infection induces CCL20 in human gastric epithelial cells remains to be determined. The aim of this study was to analyze the molecular mechanism of H. pylori-induced CCL20 expression. Expression of CCL20 mRNA was assessed by reverse transcription-PCR. Five normal and five H. pylori-infected gastric tissue samples were stained immunohistochemically for CCL20. A luciferase assay was used to monitor activation of the CCL20 gene promoter, and an electrophoretic mobility shift assay was used to explore the binding of transcription factors to this promoter. The CCL20 expression in epithelial cells of H. pylori-positive tissues was higher than that in H. pylori-negative tissues. H. pylori induced CCL20 expression in gastric epithelial cell lines, and the induction was dependent on an intact cag pathogenicity island. Activation of the CCL20 promoter by H. pylori occurred through the action of NF-kappaB. Transfection of IkappaB kinase and NF-kappaB-inducing kinase dominant negative mutants inhibited H. pylori-mediated activation of CCL20. Treatment with an inhibitor of Hsp90 suppressed H. pylori-induced CCL20 mRNA due to deactivation of NF-kappaB. Collectively, these results suggest that H. pylori activates NF-kappaB through an intracellular signaling pathway that involves IkappaB kinase and NF-kappaB-inducing kinase, leading to CCL20 gene transcription, and that Hsp90 is a crucial regulator of H. pylori-induced CCL20 expression, presumably contributing to the immune response in H. pylori.
Assuntos
Quimiocina CCL20/biossíntese , Infecções por Helicobacter/imunologia , Helicobacter pylori/imunologia , Proteínas Inflamatórias de Macrófagos/biossíntese , Regulação para Cima , Fusão Gênica Artificial , Biópsia , Linhagem Celular , Quimiocina CCL20/genética , DNA Bacteriano/metabolismo , Ensaio de Desvio de Mobilidade Eletroforética , Células Epiteliais/imunologia , Células Epiteliais/microbiologia , Mucosa Gástrica/imunologia , Mucosa Gástrica/microbiologia , Genes Reporter , Humanos , Luciferases/biossíntese , Luciferases/genética , Proteínas Inflamatórias de Macrófagos/genética , NF-kappa B/imunologia , Regiões Promotoras Genéticas/fisiologia , Ligação Proteica , RNA Mensageiro/biossíntese , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fatores de Transcrição/metabolismoAssuntos
Hemorragia Gastrointestinal/etiologia , Hemorragia Gastrointestinal/cirurgia , Pseudocisto Pancreático/complicações , Doença Crônica , Fístula Gástrica/etiologia , Fístula Gástrica/patologia , Gastroscopia , Humanos , Masculino , Pessoa de Meia-Idade , Pseudocisto Pancreático/patologia , Pancreatite/complicaçõesRESUMO
Primary biliary cirrhosis is often associated with autoimmune diseases. However, an association between primary biliary cirrhosis and pernicious anemia has rarely been reported. We report a patient with primary biliary cirrhosis associated with pernicious anemia and autoimmune gastritis. The patient was a 64-year-old Japanese woman who had been diagnosed as having primary biliary cirrhosis 5 years previously. She was readmitted with jaundice and macrocytic anemia. The diagnosis of pernicious anemia was confirmed by the low level of serum vitamin B12 and the presence of anti-parietal cell antibody and anti-intrinsic factor antibody. Pernicious anemia should be regarded as a possible complication of primary biliary cirrhosis.
