RESUMO
OBJECTIVE: To investigate the effects of Qingre Jianpi decoction (ï¼QRJPD) on dextran sulfate sodium (DSS)-induced colitis mice and explore its mechanism. METHODS: All mice were randomly divided into six groups. Weight changes, disease activity index values, and histological damage were detected. Inflammatory cytokines and immune cell infiltration were measured using enzyme-linked immunosorbent assays (ELISA) and immunohistochemistry (IHC) method. The key protein expression levels of the NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome were detected by western blot analysis, IHC, and quantitative reverse transcription polymerase chain reaction. RESULTS: QRJPD played an anti-inflammatory role in the treatment of ulcerative colitis (UC), reduced the secretion of inflammatory cytokines, and inhibited the inflammatory infiltration of immune cells by suppressing DSS-induced activation of the NLRP3 inflammasome. CONCLUSION: QRJPD exerts protective effects by inhibiting DSS-induced NLRP3 inflammasome activation.
Assuntos
Colite Ulcerativa/tratamento farmacológico , Medicamentos de Ervas Chinesas/administração & dosagem , Proteína 3 que Contém Domínio de Pirina da Família NLR/imunologia , Animais , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/genética , Colite Ulcerativa/imunologia , Sulfato de Dextrana/efeitos adversos , Humanos , Inflamassomos/efeitos dos fármacos , Inflamassomos/genética , Inflamassomos/imunologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Proteína 3 que Contém Domínio de Pirina da Família NLR/química , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Proteínas NLR/química , Proteínas NLR/genética , Proteínas NLR/imunologia , Domínio PirinaRESUMO
AIMS: In this study, we will investigate the therapeutic effects of berberine (BBR) in Helicobacter pylori (H. pylori) induced chronic atrophic gastritis (CAG). Furthermore, potential mechanisms of BBR in regulating IRF8-IFN-γ signaling axis will also be investigated. MATERIALS AND METHODS: H. pylori were utilized to establish CAG model of rats. Therapeutic effects of BBR on serum supernatant indices, and histopathology of stomach were analyzed in vivo. Moreover, GES-1 cells were infected by H. pylori, and intervened with BBR in vitro. Cell viability, morphology, proliferation, and quantitative analysis were detected by high-content screening (HCS) imaging assay. To further investigate the potential mechanisms of BBR, relative mRNA, immunohistochemistry and protein expression in IRF8-IFN-γ signaling axis were measured. KEY FINDINGS: Results showed serum supernatant indices including IL-17, CXCL1, and CXCL9 were downregulated by BBR intervention, while, G-17 increased significantly. Histological injuries of gastric mucosa induced by H. pylori also were alleviated. Moreover, cell viability and morphology changes of GES-1 cells were improved by BBR intervention. In addition, proinflammatory genes and IRF8-IFN-γ signaling axis related genes, including Ifit3, Upp1, USP18, Nlrc5, were suppressed by BBR administration in vitro and in vivo. The proteins expression related to IRF8-IFN-γ signaling axis, including Ifit3, IRF1 and Ifit1 were downregulated by BBR intervention.
Assuntos
Anti-Inflamatórios/farmacologia , Berberina/farmacologia , Gastrite Atrófica/tratamento farmacológico , Infecções por Helicobacter/tratamento farmacológico , Fatores Reguladores de Interferon/genética , Interferon gama/genética , Animais , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Quimiocina CXCL1/antagonistas & inibidores , Quimiocina CXCL1/genética , Quimiocina CXCL1/imunologia , Quimiocina CXCL9/antagonistas & inibidores , Quimiocina CXCL9/genética , Quimiocina CXCL9/imunologia , Doença Crônica , Modelos Animais de Doenças , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/imunologia , Células Epiteliais/microbiologia , Gastrite Atrófica/genética , Gastrite Atrófica/imunologia , Gastrite Atrófica/microbiologia , Regulação da Expressão Gênica , Infecções por Helicobacter/genética , Infecções por Helicobacter/imunologia , Infecções por Helicobacter/microbiologia , Helicobacter pylori/efeitos dos fármacos , Helicobacter pylori/crescimento & desenvolvimento , Helicobacter pylori/patogenicidade , Humanos , Fatores Reguladores de Interferon/antagonistas & inibidores , Fatores Reguladores de Interferon/imunologia , Interferon gama/antagonistas & inibidores , Interferon gama/imunologia , Interleucina-17/agonistas , Interleucina-17/genética , Interleucina-17/imunologia , Masculino , Proteínas NLR/antagonistas & inibidores , Proteínas NLR/genética , Proteínas NLR/imunologia , Ratos , Ratos Sprague-Dawley , Transdução de Sinais , Uridina Fosforilase/antagonistas & inibidores , Uridina Fosforilase/genética , Uridina Fosforilase/imunologiaRESUMO
Potato virus Y (PVY) is a major potato (Solanum tuberosum L.) pathogen that causes severe annual crop losses worth billions of dollars worldwide. PVY is transmitted by aphids, and successful control of virus transmission requires the extensive use of environmentally damaging insecticides to reduce vector populations. Rysto , from the wild relative S. stoloniferum, confers extreme resistance (ER) to PVY and related viruses and is a valuable trait that is widely employed in potato resistance breeding programmes. Rysto was previously mapped to a region of potato chromosome XII, but the specific gene has not been identified to date. In this study, we isolated Rysto using resistance gene enrichment sequencing (RenSeq) and PacBio SMRT (Pacific Biosciences single-molecule real-time sequencing). Rysto was found to encode a nucleotide-binding leucine-rich repeat (NLR) protein with an N-terminal TIR domain and was sufficient for PVY perception and ER in transgenic potato plants. Rysto -dependent extreme resistance was temperature-independent and requires EDS1 and NRG1 proteins. Rysto may prove valuable for creating PVY-resistant cultivars of potato and other Solanaceae crops.