Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 2 de 2
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Int Immunopharmacol ; 90: 107242, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33307514

RESUMO

Colonic patches, the counterparts of Peyer's patches in the small intestine, are dynamically regulated lymphoid tissues in the colon that have an important role in defensing against microbial infections. Berberine is an isoquinoline alkaloid extracted from medicinal herbs including Rhizoma coptidis and has long been used for the treatment of infectious gastroenteritis, but its impact on the colonic lymphoid tissues (such as colonic patches) is unknown. In this study, we aimed to investigate whether berberine had any influences on the colonic patches in mice with bacterial infection. The results showed that oral berberine administration in bacterial infected mice substantially enhanced the hypertrophy of colonic patches, which usually possessed the features of two large B-cell follicles with a separate T-cell area. Moreover, the colonic patches displayed follicular dendritic cell networks within the B-cell follicles, indicative of mature colonic patches containing germinal centers. Concomitant with enlarged colonic patches, the cultured colon of infected mice treated with berberine secreted significantly higher levels of interleukin-1ß (IL-1ß), IL-6, TNF-α, and CCL-2, while NLRP3 inhibitor MMC950 or knockout of NLRP3 gene abrogated berberine-induced hypertrophy of colonic patches, suggesting the involvement of the NLRP3 signaling pathway in this process. Functionally, oral administration of berberine ameliorated liver inflammation and improved formed feces in the colon. Altogether, these results indicated that berberine was able to augment the hypertrophy of colonic patches in mice with bacterial infection probably through enhancing local inflammatory responses in the colon.


Assuntos
Infecções Bacterianas/patologia , Berberina/uso terapêutico , Colo/efeitos dos fármacos , Tecido Linfoide/efeitos dos fármacos , Doenças Peritoneais/patologia , Animais , Linfócitos B/efeitos dos fármacos , Infecções Bacterianas/tratamento farmacológico , Infecções Bacterianas/metabolismo , Colo/crescimento & desenvolvimento , Colo/patologia , Citocinas/metabolismo , Células Dendríticas/efeitos dos fármacos , Feminino , Gastroenterite/tratamento farmacológico , Tecido Linfoide/crescimento & desenvolvimento , Tecido Linfoide/patologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Proteína 3 que Contém Domínio de Pirina da Família NLR/antagonistas & inibidores , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Doenças Peritoneais/tratamento farmacológico , Doenças Peritoneais/metabolismo , Linfócitos T/efeitos dos fármacos
2.
Cell Prolif ; 52(5): e12663, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31347748

RESUMO

OBJECTIVE: Induction of secondary necrosis/pyroptosis contributes to the toxicity of chemotherapeutic drugs, in which gasdermin E (GSDME) plays critical roles. This study aimed to explore whether GSDME is involved in mediating the cytotoxic effects of cisplatin and doxorubicin on mouse macrophages. METHODS: RAW 264.7 cells and bone marrow-derived macrophages (BMDMs) were treated with cisplatin or doxorubicin. Propidium iodide staining was used to assay necrosis, and immunoblotting was performed to detect protein expression. GSDME was knocked down by using small interfering RNA. Mice were injected intraperitoneally to evaluate toxicity to macrophages in vivo. Flow cytometry and immunofluorescence microscopy were adopted to analyse phenotypes of peritoneal cells. Cytokine levels were assayed by cytometric bead array. RESULTS: Both cisplatin and doxorubicin dose-dependently induced necrosis in mouse RAW 264.7 macrophages and BMDMs. Accompanying this, multiple caspases were activated, concomitant with the cleavage of poly (ADP-ribose) polymerase. Consistent with caspase-3 activation, GSDME was cleaved to generate its N-terminal fragment (GSDME-NT), thus leading to secondary necrosis/pyroptosis. Inhibition of caspase-3 significantly attenuated the generation of GSDME-NT concurrently with decreased necrosis in macrophages. GSDME knockdown also evidently decreased the necrosis in RAW 264.7 and BMDMs. Besides, cisplatin administration depleted peritoneal macrophages in mice, which was associated with caspase-3 activation and GSDME-NT generation. Consistent with the macrophage depletion, cisplatin administration significantly decreased survival of mice with bacterial infection. CONCLUSION: Chemotherapeutic cisplatin and doxorubicin exerted their cytotoxicity on macrophages partly by inducing caspase-3/GSDME-mediated secondary necrosis.


Assuntos
Caspase 3/metabolismo , Cisplatino/farmacologia , Doxorrubicina/farmacologia , Piroptose/efeitos dos fármacos , Receptores de Estrogênio/metabolismo , Animais , Apoptose/efeitos dos fármacos , Citocinas/metabolismo , Infecções por Escherichia coli/tratamento farmacológico , Infecções por Escherichia coli/mortalidade , Infecções por Escherichia coli/patologia , Infecções por Escherichia coli/veterinária , Macrófagos/citologia , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Células RAW 264.7 , Interferência de RNA , RNA Interferente Pequeno/metabolismo , Receptores de Estrogênio/antagonistas & inibidores , Receptores de Estrogênio/genética , Taxa de Sobrevida
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...