PMID- 18006062
OWN - NLM
STAT- MEDLINE
DCOM- 20080822
LR  - 20231213
IS  - 0161-5890 (Print)
IS  - 0161-5890 (Linking)
VI  - 45
IP  - 6
DP  - 2008 Mar
TI  - TLR4 signaling induces functional nerve growth factor receptor p75NTR on mouse 
      dendritic cells via p38MAPK and NF-kappa B pathways.
PG  - 1557-66
AB  - 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 p75(NTR) on mouse bone marrow-derived DCs (BMDCs) in vitro in dose- and 
      time-dependent manners. The expression of NGF and NGF receptor p75(NTR) 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 p75(NTR) was TLR4 
      pathway-dependent. Furthermore, LPS-induced upregulation of NGF and p75(NTR) 
      could be inhibited by p38MAPK inhibitor SB203580 and NF-kappaB inhibitor PDTC, 
      suggesting TLR4-triggered activation of p38MAPK and NF-kappaB pathways are 
      responsible for the process. Interestingly, NGF could markedly promote 
      LPS-pretreated BMDCs to secret IL-12p40 and TNF-alpha, which could be abolished 
      by pretreatment with p75(NTR) antagonist or the specific small interference RNA 
      duplex targeting p75(NTR) (p75-siRNA), suggesting the inducible p75(NTR) 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-kappaB pathways, suggesting that NGF may be involved in the 
      pathogenesis of inflammatory diseases.
FAU - Jiang, Yingming
AU  - Jiang Y
AD  - Institute of Immunology and National Key Laboratory of Medical Immunology, Second 
      Military Medical University, 800 Xiangyin Road, Shanghai 200433, People's 
      Republic of China.
FAU - Chen, Guoyou
AU  - Chen G
FAU - Zheng, Yuanyuan
AU  - Zheng Y
FAU - Lu, Lin
AU  - Lu L
FAU - Wu, Cong
AU  - Wu C
FAU - Zhang, Yi
AU  - Zhang Y
FAU - Liu, Qiuyan
AU  - Liu Q
FAU - Cao, Xuetao
AU  - Cao X
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20071119
PL  - England
TA  - Mol Immunol
JT  - Molecular immunology
JID - 7905289
RN  - 0 (Imidazoles)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (NF-kappa B)
RN  - 0 (Pyridines)
RN  - 0 (Receptors, Nerve Growth Factor)
RN  - 0 (Ngfr protein, mouse)
RN  - 0 (Thiocarbamates)
RN  - 0 (Toll-Like Receptor 4)
RN  - 135467-92-4 (prolinedithiocarbamate)
RN  - 9DLQ4CIU6V (Proline)
RN  - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
RN  - OU13V1EYWQ (SB 203580)
SB  - IM
MH  - Animals
MH  - Cell Differentiation
MH  - Dendritic Cells/cytology/*immunology
MH  - Imidazoles/pharmacology
MH  - Lipopolysaccharides/pharmacology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - NF-kappa B/antagonists & inhibitors/*immunology
MH  - Proline/analogs & derivatives/pharmacology
MH  - Pyridines/pharmacology
MH  - Receptors, Nerve Growth Factor/*biosynthesis
MH  - Signal Transduction
MH  - Thiocarbamates/pharmacology
MH  - Toll-Like Receptor 4/genetics/*immunology
MH  - p38 Mitogen-Activated Protein Kinases/antagonists & inhibitors/*metabolism
EDAT- 2007/11/17 09:00
MHDA- 2008/08/23 09:00
CRDT- 2007/11/17 09:00
PHST- 2007/09/21 00:00 [received]
PHST- 2007/10/05 00:00 [accepted]
PHST- 2007/11/17 09:00 [pubmed]
PHST- 2008/08/23 09:00 [medline]
PHST- 2007/11/17 09:00 [entrez]
AID - S0161-5890(07)00802-4 [pii]
AID - 10.1016/j.molimm.2007.10.008 [doi]
PST - ppublish
SO  - Mol Immunol. 2008 Mar;45(6):1557-66. doi: 10.1016/j.molimm.2007.10.008. Epub 2007 
      Nov 19.