Objective: To investigate the role of transduce molecules and modulatory factors of signal pathways of Toll-like receptors (TLRs) in aberrant inflammatory response in children with sepsis.
Methods: Peripheral blood mononuclear cell (PBMC) and serum were obtained from 10 children with sepsis, 13 children with severe sepsis and 17 age-matched healthy children as controls. Real-time polymerase chain reaction (real-time PCR) were used to evaluate the mRNA expression levels of TLR2, TLR4, myeloid differentiation primary response gene 88(MyD88), interleukin-1 receptor-associated kinase 4 (IRAK-4), tumor necrosis factor receptor-associated factor 6 (TRAF6), TAK1-binding protein 2 (TAB2) transforming growth factor-beta-activating kinase 1 (TAK1), interleukin-1 receptor-associated kinase 3 (IRAK-M), zinc finger protein inhibiting nuclear factor-KappaB (Triad3A), protein associated with Tlr4 (PRAT4B) and signal-transducing adaptor protein-2 (STAP2), and the levels of mRNA expression and production of pro-inflammatory cytokines [tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta) and IL-6] were measured by real-time PCR and enzyme-linked immunosorbent assay (ELISA).
Results: Compared with the healthy control group, the levels of gene expression and protein of pro-inflammatory cytokines (TNF-alpha, IL-1 beta and IL-6), the levels of gene expression of signal pathway molecules of TLRs (TLR2, TLR4, MyD88, TRAF6, IRAK4, TAK1 and TAB2) and the levels of gene expression of positive modulators of TLRs pathways (PRAT4B and STAP2) were significantly increased in sepsis group and severe sepsis group (all P < 0.01), and the levels in severe sepsis group were even higher than those in sepsis group (all P < 0.01). The mRNA expression levels of negative modulators of TLRs pathways (IRAK-M and Triad3A) were significantly elevated in sepsis group compared with those in healthy control group (all P < 0.01), but the mRNA expression levels of the negative modulators in severe sepsis group were significantly lowered compared with those in sepsis group (all P < 0.01).
Conclusion: Aberrant expression of signal pathway molecules and the modulators in TLRs signaling might play an important role on production and development of abnormal inflammatory response in children with sepsis.