Background: Increasing evidence indicates that micro RNAs(mi RNAs) are involved in inflammatory response and immune regulation following pathogen invasion. The purpose of this study was to elucidate the roles played b...Background: Increasing evidence indicates that micro RNAs(mi RNAs) are involved in inflammatory response and immune regulation following pathogen invasion. The purpose of this study was to elucidate the roles played by Gallus gallus micro RNA-1306-5 p(gga-mi R-1306-5 p) in host responses against potential invasion by Salmonella enteritidis(SE) in chickens and the underlying mechanisms.Results: In present study, the expression levels of gga-mi R-1306-5 p were determined in both tissues and HD11 cells. The results showed that gga-mi R-1306-5 p was significantly increased following SE infection or lipopolysaccharide(LPS) stimulation. The dual luciferase reporter assay further validated that gga-mi R-1306-5 p targeted the Toll-interacting protein(Tollip), and thereby participated in the regulation of immune response against SE or LPS stimulation through binding with the 3′-untranslated region(3’UTR) of Tollip. Additionally, the expression of Tollip was significantly blocked by over-expressed gga-mi R-1306-5 p. The underlying mechanisms by which ggami R-1306-5 p modulated the production of pro-inflammatory cytokines were also investigated. Molecular biological assays demonstrated that overexpression of gga-mi R-1306-5 p promoted the production of pro-inflammatory mediators, including NF-κB, TNF-α, IL-6, and IL-1β, which produced effects similar to those of Tollip knockdown.Conclusions: Taken together, gga-mi R-1306-5 p induced by SE or LPS, regulates the immune response by inhibiting Tollip, which activates the production of inflammatory cytokines. This study has provided the first direct evidence that gga-mi R-1306-5 p targets Tollip, and is involved in the host response against SE.展开更多
Toll-like receptors (TLR) are essential for Helicobacter pylori (Hp) recognition and subsequent innate and adaptive immunity responses. TLR2 appears to be the receptor responsible for most of the immunologic reaction ...Toll-like receptors (TLR) are essential for Helicobacter pylori (Hp) recognition and subsequent innate and adaptive immunity responses. TLR2 appears to be the receptor responsible for most of the immunologic reaction against Hp infection. However, TLR4, TLR9 and eventually TLR5 may also have a synergic effect with TLR2 against Hp. It has been shown that gastric Hp infection increases TLR expression in the gastric mucosa. Moreover, recent studies have shown that human gastric carcinogenesis is associated not only with increased expression of TLR but also with decreased expression of their inhibitors such as Toll-Interacting Protein (TOLLIP) and peroxisome proliferator-activated receptor (PPAR)-g. Indeed, gastric dysplasia and adenocarcinoma are associated with high expression levels of TLR and low levels of TOLLIP and PPAR-g, suggesting increased activation of these receptors throughout human gastric carcinogenesis. In this article we discuss how these novels findings could be used not only for the diagnosis and prognosis of gastric lesions associated with Hp infection but also for their treatment. Specifically, we discuss the potential use of TLR agonists in addition to antibiotics to improve eradication rates of Hp and of TLR antagonists to slow the progression of gastric preneoplastic lesions. We also discuss the potential value of TLR signalling blockers and quantification of tumoral TLR expression, respectively, in the treatment and prognosis of gastric cancer. In conclusion, TLRs can be an important link between Hp and the sequence of gastric carcinogenesis and they can be used as biomarkers of gastric carcinogenesis. In this article, future lines of investigation related with these novel scientific findings are proposed and discussed.展开更多
基金supported by grants from the National Natural Science Foundation of China(No.31572393)the National Key Technology R&D Program(2015BAD03B03)+1 种基金the China Agricultural Science and Technology Innovation Project(ASTIPIAS04)the earmarked fund for Modern AgroIndustry Technology Research System(CARS-41)
文摘Background: Increasing evidence indicates that micro RNAs(mi RNAs) are involved in inflammatory response and immune regulation following pathogen invasion. The purpose of this study was to elucidate the roles played by Gallus gallus micro RNA-1306-5 p(gga-mi R-1306-5 p) in host responses against potential invasion by Salmonella enteritidis(SE) in chickens and the underlying mechanisms.Results: In present study, the expression levels of gga-mi R-1306-5 p were determined in both tissues and HD11 cells. The results showed that gga-mi R-1306-5 p was significantly increased following SE infection or lipopolysaccharide(LPS) stimulation. The dual luciferase reporter assay further validated that gga-mi R-1306-5 p targeted the Toll-interacting protein(Tollip), and thereby participated in the regulation of immune response against SE or LPS stimulation through binding with the 3′-untranslated region(3’UTR) of Tollip. Additionally, the expression of Tollip was significantly blocked by over-expressed gga-mi R-1306-5 p. The underlying mechanisms by which ggami R-1306-5 p modulated the production of pro-inflammatory cytokines were also investigated. Molecular biological assays demonstrated that overexpression of gga-mi R-1306-5 p promoted the production of pro-inflammatory mediators, including NF-κB, TNF-α, IL-6, and IL-1β, which produced effects similar to those of Tollip knockdown.Conclusions: Taken together, gga-mi R-1306-5 p induced by SE or LPS, regulates the immune response by inhibiting Tollip, which activates the production of inflammatory cytokines. This study has provided the first direct evidence that gga-mi R-1306-5 p targets Tollip, and is involved in the host response against SE.
基金National Natural Science Foundation of China(Grant No.81573602)the Project of Science and Technology for Chinese Medicine of Zhejiang Province,China(Grant No.2013KYB183)+1 种基金the Chinese Medicine Research Program of Zhejiang Province,China(Grant No.2014ZQ008,2016ZA183,2015ZQ011)Zhejiang Province Association of Traditional Chinese Medcine(Grant No.2013103)
文摘Toll-like receptors (TLR) are essential for Helicobacter pylori (Hp) recognition and subsequent innate and adaptive immunity responses. TLR2 appears to be the receptor responsible for most of the immunologic reaction against Hp infection. However, TLR4, TLR9 and eventually TLR5 may also have a synergic effect with TLR2 against Hp. It has been shown that gastric Hp infection increases TLR expression in the gastric mucosa. Moreover, recent studies have shown that human gastric carcinogenesis is associated not only with increased expression of TLR but also with decreased expression of their inhibitors such as Toll-Interacting Protein (TOLLIP) and peroxisome proliferator-activated receptor (PPAR)-g. Indeed, gastric dysplasia and adenocarcinoma are associated with high expression levels of TLR and low levels of TOLLIP and PPAR-g, suggesting increased activation of these receptors throughout human gastric carcinogenesis. In this article we discuss how these novels findings could be used not only for the diagnosis and prognosis of gastric lesions associated with Hp infection but also for their treatment. Specifically, we discuss the potential use of TLR agonists in addition to antibiotics to improve eradication rates of Hp and of TLR antagonists to slow the progression of gastric preneoplastic lesions. We also discuss the potential value of TLR signalling blockers and quantification of tumoral TLR expression, respectively, in the treatment and prognosis of gastric cancer. In conclusion, TLRs can be an important link between Hp and the sequence of gastric carcinogenesis and they can be used as biomarkers of gastric carcinogenesis. In this article, future lines of investigation related with these novel scientific findings are proposed and discussed.
