Toll-like receptors （TLRs） are sentinels of the host defense system, which recognize a large number of microbial pathogens. The host defense system may be inefficient or inflammatory diseases may develop if microbia...Toll-like receptors （TLRs） are sentinels of the host defense system, which recognize a large number of microbial pathogens. The host defense system may be inefficient or inflammatory diseases may develop if microbial recognition by TLRs and subsequent TLR-triggered cytokine production are deregulated. Activating transcription factor 4 （ATF4）, a member of the ATF/CREB transcription factor family, is an important factor that participates in several pathophysiological processes. In this report, we found that ATF4 is also involved in the TLR-mediated innate immune response, which participates in TLR4 signal transduction and mediates the secretion of a variety of cytokines. We observed that ATF4 is activated and translocates to the nucleus following l ipopolysaccharide （LPS） stimulation via the TLR4-MyD88-dependent pathway. Additionally, a cytokine array assay showed that some key inflammatory cytokines, such as I L-6, I L-8 and RANTES, are positively regulated by ATF4. We also demonstrate that c-Jun directly binds to ATF4, thereby promoting the secretion of inflammatory cytokines. Taken together, these results indicate that ATF4 acts as a positive regulator in TLR4-triggered cytokine production.展开更多
Objective To investigate the effect of C/EBP homologous protein (CHOP) on mRNA expressions of RNA-dependent protein kinase-like ER kinase (PERK)-activating transcription factor 4 (ATF4)-C/EBP homologous protein (CHOP)...Objective To investigate the effect of C/EBP homologous protein (CHOP) on mRNA expressions of RNA-dependent protein kinase-like ER kinase (PERK)-activating transcription factor 4 (ATF4)-C/EBP homologous protein (CHOP) pathway in diabetic peripheral neuropathy(DPN) rats. Methods 48 SD male rats werefed with high-fat diet combined with intraperitoneal injectionof streptozotocin to replicate DPN Model. Then allthe rats were divided into control group (Con),control +CHOP siRNA group ( Con + CHOPsiRNA ), Modelcontrol group (Mod) and CHOP siRNA group. Transfectionreagent and CHOP siRNA were intrathecally injected.展开更多
文摘Toll-like receptors （TLRs） are sentinels of the host defense system, which recognize a large number of microbial pathogens. The host defense system may be inefficient or inflammatory diseases may develop if microbial recognition by TLRs and subsequent TLR-triggered cytokine production are deregulated. Activating transcription factor 4 （ATF4）, a member of the ATF/CREB transcription factor family, is an important factor that participates in several pathophysiological processes. In this report, we found that ATF4 is also involved in the TLR-mediated innate immune response, which participates in TLR4 signal transduction and mediates the secretion of a variety of cytokines. We observed that ATF4 is activated and translocates to the nucleus following l ipopolysaccharide （LPS） stimulation via the TLR4-MyD88-dependent pathway. Additionally, a cytokine array assay showed that some key inflammatory cytokines, such as I L-6, I L-8 and RANTES, are positively regulated by ATF4. We also demonstrate that c-Jun directly binds to ATF4, thereby promoting the secretion of inflammatory cytokines. Taken together, these results indicate that ATF4 acts as a positive regulator in TLR4-triggered cytokine production.
文摘Objective To investigate the effect of C/EBP homologous protein (CHOP) on mRNA expressions of RNA-dependent protein kinase-like ER kinase (PERK)-activating transcription factor 4 (ATF4)-C/EBP homologous protein (CHOP) pathway in diabetic peripheral neuropathy(DPN) rats. Methods 48 SD male rats werefed with high-fat diet combined with intraperitoneal injectionof streptozotocin to replicate DPN Model. Then allthe rats were divided into control group (Con),control +CHOP siRNA group ( Con + CHOPsiRNA ), Modelcontrol group (Mod) and CHOP siRNA group. Transfectionreagent and CHOP siRNA were intrathecally injected.
