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- W2024169595 abstract "Many neuropeptides that are produced by immune cells have been shown to be involved in the pathogenesis of immunological disorders. Nerve growth factor (NGF) and its receptors are found to be widely expressed in the immune system and regulate both innate and adaptive immune responses. However, the underlying mechanisms by which NGF contributes to pathogenesis of inflammatory diseases remain to be fully understood. Dendritic cells (DCs) are potent initiator for inflammatory and immune responses upon recognization and activation of Toll-like receptors (TLRs). In this study, we demonstrated that stimulation with TLR ligand lipopolysaccharide (LPS), but not lipoteichoic acid (LTA), Poly (I:C) and CpG oligodeoxynucleotide (ODN), could significantly induce expression of NGF and NGF receptor p75NTR on mouse bone marrow-derived DCs (BMDCs) in vitro in dose- and time-dependent manners. The expression of NGF and NGF receptor p75NTR also increased on splenic DCs isolated from the mice injected with LPS in vivo. However, there was no such effect on DCs derived from TLR4-deficient mice, indicating the LPS-induced upregulation of NGF and p75NTR was TLR4 pathway-dependent. Furthermore, LPS-induced upregulation of NGF and p75NTR could be inhibited by p38MAPK inhibitor SB203580 and NF-κB inhibitor PDTC, suggesting TLR4-triggered activation of p38MAPK and NF-κB pathways are responsible for the process. Interestingly, NGF could markedly promote LPS-pretreated BMDCs to secret IL-12p40 and TNF-α, which could be abolished by pretreatment with p75NTR antagonist or the specific small interference RNA duplex targeting p75NTR (p75-siRNA), suggesting the inducible p75NTR is critical for the TLR4-initiated inflammatory effect of NGF on BMDCs. Thus, TLR4 signaling can induce expression of NGF and p75 NTR on DCs via activation of p38 MAPK and NF-κB pathways, suggesting that NGF may be involved in the pathogenesis of inflammatory diseases." @default.
- W2024169595 created "2016-06-24" @default.
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- W2024169595 date "2008-03-01" @default.
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- W2024169595 title "TLR4 signaling induces functional nerve growth factor receptor p75NTR on mouse dendritic cells via p38MAPK and NF-κB pathways" @default.
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- W2024169595 doi "https://doi.org/10.1016/j.molimm.2007.10.008" @default.
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