Duction of tumour necrosis factor-a induced by LPS plus CpG ODN.

Duction of tumour necrosis factor-a induced by LPS plus CpG ODN. Whilst inhibition of extracellular signal-related kinase and NF-kB activation suppressed the up-regulation of the expression of TLR2, TLR4 and TLR9 mRNA, inhibition of p38 kinase prevented the up-regulation of TLR2 and TLR4 mRNA expression but enhanced the up-regulation of TLR9 expression. These final results demonstrated that TLR2, TLR4 and TLR9 gene expression was differently regulated by LPS in mouse immature DC. Up-regulation of TLR2, TLR4 and TLR9 expression by LPS might promote the overall responses of DC to bacteria and assist to clarify the synergy amongst LPS as well as other bacterial products in the induction of cytokine production.INTRODUCTION Dendritic cells (DC), because the most potent qualified antigen-presenting cells, are critical sentinels in antimicrobial immune responses. Microbial solutions, including lipopolysaccharide (LPS) and bacterial DNA, can activateReceived three July 2001; revised 21 January 2002; accepted 30 January 2002. Abbreviations: CpG ODN, CpG-containing oligonucleotides; DC, dendritic cells; ERK, extracellular signal-regulated kinase; LPS, lipopolysaccharide; MAPK, mitogen-activated protein kinase; PAMP, pathogen-associated molecule patterns; PDTC, pyrrolidinecarbodithioic acid; TLR, toll-like receptor. Correspondence: Dr Xuetao Cao, Institute of Immunology, Second Military Healthcare University, 800 Xiangyin Road, Shanghai 200433, China. E-mail: [email protected] DC and induce DC maturation, characterized by production of cytokines, up-regulation of co-stimulatory molecules and improved capability to activate T cells.1 Cells on the innate immune system use various pathogenassociated molecule pattern (PAMP) recognition receptors to recognize the patterns shared among pathogens.1,two Nevertheless, the mechanisms by which the microbial products are recognized by immune cells plus the signals are transmitted to induce downstream events have not been completely understood. Not too long ago, Toll-like receptors (TLR) have been identified as major recognition receptors for PAMP which include LPS, peptidoglycan, lipoteichoic acid and CpG-containing oligonucleotides (CpG ODN).Palivizumab 3 Toll, very first identified as a crucial protein controlling dorsoventral pattern formation during the early improvement of Drosophila melanogaster, is really a transmembrane protein whose intracellular portion#2002 Blackwell Science LtdRegulation of TLR expression by LPS in DCis homologous to that of interleukin-1 receptor (IL-1R) loved ones proteins.Fluralaner 6 It has been shown that Toll participates in antimicrobial immune responses in adult Drosophila.PMID:32472497 7 Activation of Toll final results in the initiation of a signalling cascade homologous to that activated by IL-1R in mammalian cells and also the production from the antifungal peptide, drosomycin.7 Toll is conserved throughout different species. In addition to cytoplasmic portion homologues to IL-1R, all mammalian TLR loved ones members share repeating leucine-rich motifs in their extracellular portions, which interact with and recognize PAMP.two,six Up to now, ten TLRs have been identified inside the human.8 Amongst them, TLR2 and TLR4 have been studied intensively. Genetic analysis of hyposensitive mouse C3H/HeJ identified TLR4 as a key receptor for LPS.4,9 However, TLR2-deficient mice failed to respond to Gram-positive cell wall components but remained responsive to LPS.ten,11 Having said that, these data do not rule out a achievable function of TLR2 as a helper receptor for TLR4 in signalling to LPS also.