PMID- 14568957
OWN - NLM
STAT- MEDLINE
DCOM- 20040130
LR  - 20201222
IS  - 0022-1767 (Print)
IS  - 0022-1767 (Linking)
VI  - 171
IP  - 9
DP  - 2003 Nov 1
TI  - Novel and detrimental effects of lipopolysaccharide on in vitro generation of 
      immature dendritic cells: involvement of mitogen-activated protein kinase p38.
PG  - 4792-800
AB  - Dendritic cells (DCs) are recognized as major players in the regulation of immune 
      responses to a variety of Ags, including bacterial agents. LPS, a Gram-negative 
      bacterial cell wall component, has been shown to fully activate DCs both in vitro 
      and in vivo. LPS-induced DC maturation involves activation of p38, extracellular 
      signal-regulated kinase (ERK)/mitogen-activated protein kinases, and NF-kappaB. 
      Blocking p38 inhibits LPS-induced maturation of DCs. In this study we 
      investigated the role of LPS in the in vitro generation of immature DCs. We 
      report here that in contrast to the observed beneficial effects on DCs, the 
      presence of LPS in monocyte culture retarded the generation of immature DCs. LPS 
      not only impaired the morphology and reduced the yields of the cultured cells, 
      but also inhibited the up-regulation of surface expression of CD1a, costimulatory 
      and adhesion molecules. Furthermore, LPS up-regulated the secretion of IL-1beta, 
      IL-6, IL-8, IL-10, and TNF-alpha; reduced Ag presentation capacity; and inhibited 
      phosphorylation of ERK, but activated p38, leading to a reduced NF-kappaB 
      activity in treated cells. Neutralizing Ab against IL-10, but not other 
      cytokines, partially blocked the effects of LPS. Inhibiting p38 (by inhibitor 
      SB203580) restored the morphology, phenotype, and Ag presentation capacity of 
      LPS-treated cells. SB203580 also inhibited LPS-induced production of IL-1beta, 
      IL-10, and TNF-alpha; enhanced IL-12 production; and recovered the activity of 
      ERK and NF-kappaB. Thus, our study reveals that LPS has dual effects on DCs that 
      are biologically important: activating existing DCs to initiate an immune 
      response, and inhibiting the generation of new DCs to limit such a response.
FAU - Xie, Jin
AU  - Xie J
AD  - Myeloma Institute for Research and Therapy and Arkansas Cancer Research Center, 
      Little Rock 72205, USA.
FAU - Qian, Jianfei
AU  - Qian J
FAU - Wang, Siqing
AU  - Wang S
FAU - Freeman, Muta E 3rd
AU  - Freeman ME 3rd
FAU - Epstein, Joshua
AU  - Epstein J
FAU - Yi, Qing
AU  - Yi Q
LA  - eng
GR  - P01CA55819/CA/NCI NIH HHS/United States
GR  - R01CA96569/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Immunol
JT  - Journal of immunology (Baltimore, Md. : 1950)
JID - 2985117R
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Growth Inhibitors)
RN  - 0 (Imidazoles)
RN  - 0 (Immune Sera)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (NF-kappa B)
RN  - 0 (Pyridines)
RN  - 0 (STAT3 Transcription Factor)
RN  - 0 (STAT3 protein, human)
RN  - 0 (Trans-Activators)
RN  - 130068-27-8 (Interleukin-10)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
RN  - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
RN  - OU13V1EYWQ (SB 203580)
SB  - IM
MH  - Cell Differentiation/*drug effects/*immunology
MH  - Cells, Cultured
MH  - DNA-Binding Proteins/biosynthesis
MH  - Dendritic Cells/*enzymology/*immunology/pathology
MH  - Down-Regulation/drug effects/immunology
MH  - Enzyme Activation/drug effects/immunology
MH  - Enzyme Inhibitors/pharmacology
MH  - Growth Inhibitors/antagonists & inhibitors/*toxicity
MH  - Humans
MH  - Imidazoles/pharmacology
MH  - Immune Sera/pharmacology
MH  - Immunophenotyping
MH  - Interleukin-10/antagonists & inhibitors/immunology
MH  - Lipopolysaccharides/antagonists & inhibitors/*pharmacology/toxicity
MH  - Mitogen-Activated Protein Kinases/antagonists & inhibitors/*physiology
MH  - Monocytes/cytology/enzymology/immunology
MH  - NF-kappa B/antagonists & inhibitors/biosynthesis
MH  - Pyridines/pharmacology
MH  - STAT3 Transcription Factor
MH  - Signal Transduction/drug effects/immunology
MH  - Trans-Activators/biosynthesis
MH  - Up-Regulation/drug effects/immunology
MH  - p38 Mitogen-Activated Protein Kinases
EDAT- 2003/10/22 05:00
MHDA- 2004/01/31 05:00
CRDT- 2003/10/22 05:00
PHST- 2003/10/22 05:00 [pubmed]
PHST- 2004/01/31 05:00 [medline]
PHST- 2003/10/22 05:00 [entrez]
AID - 10.4049/jimmunol.171.9.4792 [doi]
PST - ppublish
SO  - J Immunol. 2003 Nov 1;171(9):4792-800. doi: 10.4049/jimmunol.171.9.4792.