PMID- 15477228
OWN - NLM
STAT- MEDLINE
DCOM- 20050418
LR  - 20240109
IS  - 0953-8178 (Print)
IS  - 0953-8178 (Linking)
VI  - 16
IP  - 12
DP  - 2004 Dec
TI  - Role of c-Jun N-terminal kinase on lipopolysaccharide induced maturation of human 
      monocyte-derived dendritic cells.
PG  - 1701-9
AB  - Dendritic cells (DCs) are potent antigen-presenting cells that play a pivotal 
      role in the initiation of T cell-dependent immune responses. Immature DCs 
      obtained from peripheral blood CD14+ monocytes by culture with granulocyte 
      macrophage-colony stimulating factor (GM-CSF) and interleukin-4 (IL-4) 
      differentiate into mature DCs upon stimulation with lipopolysaccharide (LPS). At 
      least three families of mitogen-activated protein kinases (MAPKs), that is, 
      extracellular signal-regulated kinases (ERK), c-Jun N-terminal kinases (JNK) and 
      p38 MAPK, are involved in the DC maturation process. We report investigations of 
      the role of JNK in the maturation of human monocyte-derived DCs. SP600125, a 
      specific inhibitor of JNK, inhibited the LPS-induced up-regulation of CD80, CD83, 
      CD86 and CD54, but augmented the up-regulation of HLA-DR. SP600125 slightly 
      inhibited the down-regulation of FITC-dextran uptake during DC maturation. 
      However, SP600125 did not affect the LPS induced up-regulation of allostimulatory 
      capacity of DCs. SP600125 inhibited the release of IL-12 p70 and TNF-alpha from 
      mature DCs. Although autologous T cells primed by the ovalbumin (OVA)-pulsed 
      mature DCs produced IFN-gamma, but not IL-4, OVA-pulsed SP600125-treated mature 
      DCs could initiate IL-4 production from autologous T cells. In contrast, a p38 
      MAPK inhibitor, SB203580, profoundly inhibited the phenotypic and functional 
      maturation of DCs, while an ERK inhibitor, PD98059, had little or no effect. 
      Taken together, the JNK signaling pathway appears to have a role that is distinct 
      from the p38 MAPK and ERK cascades in the maturation process of DCs, and may be 
      involved in the augmentation of Th2-prone T cell responses when it is suppressed.
FAU - Nakahara, Takeshi
AU  - Nakahara T
AD  - Department of Dermatology, Graduate School of Medical Sciences, Kyushu 
      University, Japan. nakahara@dermatol.med.kyushu-u.ac.jp
FAU - Uchi, Hiroshi
AU  - Uchi H
FAU - Urabe, Kazunori
AU  - Urabe K
FAU - Chen, Qijie
AU  - Chen Q
FAU - Furue, Masutaka
AU  - Furue M
FAU - Moroi, Yoichi
AU  - Moroi Y
LA  - eng
PT  - Journal Article
DEP - 20041011
PL  - England
TA  - Int Immunol
JT  - International immunology
JID - 8916182
RN  - 0 (Anthracenes)
RN  - 0 (Antigens, CD)
RN  - 0 (Cyclic AMP Response Element-Binding Protein)
RN  - 0 (Dextrans)
RN  - 0 (Flavonoids)
RN  - 0 (HLA-DR Antigens)
RN  - 0 (Imidazoles)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Protein Kinase Inhibitors)
RN  - 0 (Protein Subunits)
RN  - 0 (Pyridines)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 0 (fluorescein isothiocyanate dextran)
RN  - 187348-17-0 (Interleukin-12)
RN  - 1TW30Y2766 (pyrazolanthrone)
RN  - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases)
RN  - EC 2.7.11.24 (JNK Mitogen-Activated Protein Kinases)
RN  - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
RN  - I223NX31W9 (Fluorescein-5-isothiocyanate)
RN  - OU13V1EYWQ (SB 203580)
RN  - SJE1IO5E3I (2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one)
SB  - IM
MH  - Anthracenes/pharmacology
MH  - Antigens, CD/metabolism
MH  - Biological Transport/drug effects
MH  - Cell Differentiation/drug effects
MH  - Cells, Cultured
MH  - Cyclic AMP Response Element-Binding Protein/metabolism
MH  - Dendritic Cells/*enzymology/immunology
MH  - Dextrans/metabolism
MH  - Extracellular Signal-Regulated MAP Kinases/antagonists & inhibitors/physiology
MH  - Flavonoids/pharmacology
MH  - Fluorescein-5-isothiocyanate/*analogs & derivatives/metabolism
MH  - HLA-DR Antigens/metabolism
MH  - Humans
MH  - Imidazoles/pharmacology
MH  - Interleukin-12/metabolism
MH  - JNK Mitogen-Activated Protein Kinases/antagonists & inhibitors/*physiology
MH  - Lipopolysaccharides/pharmacology
MH  - Monocytes/drug effects
MH  - Phosphorylation
MH  - Protein Kinase Inhibitors/pharmacology
MH  - Protein Subunits/metabolism
MH  - Pyridines/pharmacology
MH  - Tumor Necrosis Factor-alpha/metabolism
MH  - Up-Regulation
MH  - p38 Mitogen-Activated Protein Kinases/antagonists & inhibitors/physiology
EDAT- 2004/10/13 09:00
MHDA- 2005/04/19 09:00
CRDT- 2004/10/13 09:00
PHST- 2004/10/13 09:00 [pubmed]
PHST- 2005/04/19 09:00 [medline]
PHST- 2004/10/13 09:00 [entrez]
AID - dxh171 [pii]
AID - 10.1093/intimm/dxh171 [doi]
PST - ppublish
SO  - Int Immunol. 2004 Dec;16(12):1701-9. doi: 10.1093/intimm/dxh171. Epub 2004 Oct 
      11.