RESUMO
Evidence indicates that macrophages play an important role in the immune system. Therefore, research involving inflammatory and oxidative stress responses in macrophages is of great significance. Many factors contribute to inflammation and oxidative stress, including Salmonella. We investigated the effect of the miR-139-5p/TRAF6 axis on the inflammatory and oxidative stress responses of Salmonella -infected macrophages. Our findings revealed that miR-139-5p decreased IL-1ß and TNF-α levels to inhibit Salmonella-induced inflammatory responses in the RAW264.7 macrophage cell line. Furthermore, miR-139-5p inhibited Salmonella-induced oxidative stress by strengthening SOD, CAT and GSH-PX activity, as well as lowering the malondialdehyde level in the RAW264.7 macrophages cell line. Subsequently, it was verified that TRAF6 was a downstream target of miR-139-5p in RAW264.7 cells. Rescue assays indicated that the over-expression of miR-139-5p inhibits the effects of TRAF6 on inflammatory and oxidative stress responses including Salmonella infection in RAW264.7 cells. To our knowledge, this study is the first to verify that miR-139-5p inhibits inflammatory and oxidative stress responses of Salmonella-infected macrophages through regulating TRAF6. This discovery may offer new insights on inflammatory and oxidative stress responses in macrophages.
Assuntos
Interações Hospedeiro-Patógeno/genética , MicroRNAs/genética , Salmonella typhimurium/genética , Fator 6 Associado a Receptor de TNF/genética , Animais , Pareamento de Bases , Sequência de Bases , Catalase/genética , Catalase/metabolismo , Regulação da Expressão Gênica , Glutationa Peroxidase/genética , Glutationa Peroxidase/metabolismo , Interleucina-1beta/genética , Interleucina-1beta/metabolismo , Lipopolissacarídeos/farmacologia , Malondialdeído/metabolismo , Camundongos , MicroRNAs/agonistas , MicroRNAs/antagonistas & inibidores , MicroRNAs/metabolismo , Mimetismo Molecular , Oligorribonucleotídeos/genética , Oligorribonucleotídeos/metabolismo , Estresse Oxidativo , Células RAW 264.7 , Salmonella typhimurium/efeitos dos fármacos , Salmonella typhimurium/crescimento & desenvolvimento , Salmonella typhimurium/metabolismo , Transdução de Sinais , Superóxido Dismutase/genética , Superóxido Dismutase/metabolismo , Fator 6 Associado a Receptor de TNF/metabolismo , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismoRESUMO
BACKGROUND: Anti-tumour necrosis factor (TNF)-α drugs are used by increasing numbers of reproductive-age women. Although the neonatal outcomes have been described, there are concerns regarding the risk of infection in offspring following exposure to anti-TNF-α. METHODS: A literature search was conducted using Pubmed, EMBASE, and the Cochrane Database, from inception through August 2020. We evaluated the risk of infection in autoimmune disease (AID) offspring unexposed to anti-TNF-α compared to AID offspring exposed to anti-TNF-α, as well as to unexposed non-AID offspring. RESULTS: Our primary analysis showed that both AID offspring unexposed to anti-TNF-α [risk ratio (RR) 1.09; 95% confidence interval (CI), 1.03-1.16; I2=0%] and AID offspring exposed to anti-TNF-α (RR 1.39; 95% CI, 1.2-1.61; I2=0%] was associated with an increased risk of infection during the first year of life compared with the unexposed non-AID offspring. However, our secondary analysis demonstrated that AID offspring exposed to anti-TNF-α was not associated with an increased risk of infection when compared with AID offspring unexposed to anti-TNF-α (RR=1.1; 95% CI, 0.86-1.4). CONCLUSION: Our results suggest that in utero exposure to anti-TNF-α does not appear to increase the risk of infection during the first year of life in the offspring; however, AID itself was associated with a marked excess risk of infection in the children.