Role Of Regulatory Factors Of Signal Pathways Of Toll-like Receptor In Inflammatory Response Of Children With Sepsis

ObjectiveTo investigate role of positive regulatory factors (PRAT4B and STAP2) and negative regulatory factors (IRAK-M, Triad3A, SIGIRR, DAP12 and FLN29) of signal pathways of Toll-like receptors (TLRs) in aberrant inflammatory response of children with sepsis.MethodsPeripheral blood mononuclear cell(PBMC) and blood plasma were obtained from 10 children with sepsis, 13 children with severe sepsis and 17 age-matched healthy child controls. Reverse-transcription PCR(RT-PCR) and real time-PCR were used to evaluated the mRNA expression levels of TLR2, TLR4, MyD88, IRAK-4, TRAF6, TAB2, TAK1, SIGIRR, IRAK-M, Triad3A, DAP12, FLN29, PRAT4B and STAP2, and the levels of expression and production of pro-inflammatory cytokine(IL-1β, IL-6 and TNF-α) mRNA were measured by RT-PCR, real-time PCR and Enzyme-Linked Immunosorbnent Assay(ELISA).Results1) Compared with the healthy control groups, the levels of gene expression and protein of pro-inflammatory cytokine(IL-1β, IL-6 and TNF-α) were significantly increased in sepsis groups and severe sepsis groups(P<0.01), while the expression levels of pro-inflammatory cytokine(IL-1β, IL-6 and TNF-α) in severe sepsis groups were higher than those in sepsis groups(P<0.05).2) Compared with the healthy control groups, the levels of mRNA expression of signal pathway molecule of TLRs (TLR2, TLR4, MyD88, TRAF6, IRAK4, TAB2 and TAK1) were significantly increased in sepsis groups and severe sepsis groups(P<0.01), while the expression levels of these signal pathway molecule of TLRs in severe sepsis groups were higher than those in sepsis groups(P<0.05).3) Compared with the healthy control groups, the mRNA expression levels of positive regulator of TLRs pathways(PRAT4B and STAP2) were significantly increased in sepsis groups and severe sepsis groups(P<0.01), while the expression levels of these positive regulator in severe sepsis groups were higher than those in sepsis groups(P<0.05).4) Compared with the healthy control groups, the mRNA expression levels of negative regulator of TLRs pathways(IRAK-M, SIGIRR, Triad3A, DAP12 and FLN29) were significantly increased in sepsis groups and severe sepsis groups(P<0.01), but the expression levels of these negative regulator in severe sepsis groups were significantly decreased than those in sepsis groups(P<0.05).ConclusionsAberrant activation of TLRs pathways may result in overexpression of pro-inflammatory cytokine, and aberrant expression of the regulators in TLR-like receptor signaling might play important role on production and development of abnormal inflammatory response in children with sepsis.