PMID- 12170268
OWN - NLM
STAT- MEDLINE
DCOM- 20020920
LR  - 20231213
IS  - 0091-6749 (Print)
IS  - 0091-6749 (Linking)
VI  - 110
IP  - 2
DP  - 2002 Aug
TI  - The sesquiterpene lactone parthenolide inhibits LPS- but not TNF-alpha-induced 
      maturation of human monocyte-derived dendritic cells by inhibition of the p38 
      mitogen-activated protein kinase pathway.
PG  - 269-76
AB  - BACKGROUND: Dendritic cells (DCs) are the most potent antigen-presenting cells, 
      and the manipulation of DC maturation provides a strategy for the treatment of 
      allergic and inflammatory diseases. OBJECTIVE: In this study we examined the 
      effect of the anti-inflammatory sesquiterpene lactone parthenolide (PTL) on DC 
      maturation induced by LPS or TNF-alpha. METHODS: Human monocyte-derived DCs 
      generated by means of culture with GM-CSF and IL-4 were pretreated with PTL and 
      subsequently stimulated with LPS or TNF-alpha. RESULTS: PTL inhibited the 
      upregulation of CD80, CD83, CD86, CD40, and MHC class II; the allostimulatory 
      function; the production of TNF-alpha and IL-12; and the downregulation of 
      FITC-labeled dextran uptake in human monocyte-derived DCs stimulated with LPS but 
      not with TNF-alpha. The inhibitory effect of PTL on DC maturation was preceded by 
      inhibition of the phosphorylation of p38 mitogen-activated protein kinase but not 
      the nuclear translocation of NF-kappaB. CONCLUSION: These results might offer PTL 
      not only as a promising compound for the treatment of LPS-induced disorders, 
      including sepsis or septic shock, by inhibition of excessive DC maturation but 
      also as a tool to further dissect the signaling pathways involved in DC 
      maturation.
FAU - Uchi, Hiroshi
AU  - Uchi H
AD  - Division of Immunology and Allergology, University of Geneva, Geneva, 
      Switzerland.
FAU - Arrighi, Jean-Francois
AU  - Arrighi JF
FAU - Aubry, Jean-Pierre
AU  - Aubry JP
FAU - Furue, Masutaka
AU  - Furue M
FAU - Hauser, Conrad
AU  - Hauser C
LA  - eng
PT  - Journal Article
PL  - United States
TA  - J Allergy Clin Immunol
JT  - The Journal of allergy and clinical immunology
JID - 1275002
RN  - 0 (Anti-Inflammatory Agents, Non-Steroidal)
RN  - 0 (Antigens, CD)
RN  - 0 (Antigens, CD1)
RN  - 0 (B7-1 Antigen)
RN  - 0 (B7-2 Antigen)
RN  - 0 (CD1a antigen)
RN  - 0 (CD40 Antigens)
RN  - 0 (CD86 protein, human)
RN  - 0 (Histocompatibility Antigens Class II)
RN  - 0 (I-kappa B Proteins)
RN  - 0 (Immunoglobulins)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (NF-kappa B)
RN  - 0 (Sesquiterpenes)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 187348-17-0 (Interleukin-12)
RN  - 2RDB26I5ZB (parthenolide)
RN  - EC 2.7.10.1 (Protein-Tyrosine Kinases)
RN  - EC 2.7.11.17 (Calcium-Calmodulin-Dependent Protein Kinases)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
RN  - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
RN  - EC 2.7.12.2 (MAP Kinase Kinase 3)
RN  - EC 2.7.12.2 (MAP Kinase Kinase 6)
RN  - EC 2.7.12.2 (MAP2K3 protein, human)
RN  - EC 2.7.12.2 (MAP2K6 protein, human)
RN  - EC 2.7.12.2 (Mitogen-Activated Protein Kinase Kinases)
SB  - IM
MH  - Anti-Inflammatory Agents, Non-Steroidal/*pharmacology
MH  - Antigens, CD/biosynthesis
MH  - Antigens, CD1/biosynthesis
MH  - B7-1 Antigen/biosynthesis
MH  - B7-2 Antigen
MH  - Biological Transport
MH  - CD40 Antigens/biosynthesis
MH  - Calcium-Calmodulin-Dependent Protein Kinases/metabolism
MH  - Cell Differentiation
MH  - Cells, Cultured
MH  - Dendritic Cells/cytology/*drug effects/metabolism
MH  - Down-Regulation
MH  - Endocytosis/drug effects
MH  - Histocompatibility Antigens Class II/biosynthesis
MH  - Humans
MH  - I-kappa B Proteins/metabolism
MH  - Immunoglobulins/biosynthesis
MH  - Interleukin-12/metabolism
MH  - Lipopolysaccharides/*pharmacology
MH  - MAP Kinase Kinase 3
MH  - MAP Kinase Kinase 6
MH  - *MAP Kinase Signaling System
MH  - Membrane Glycoproteins/biosynthesis
MH  - Mitogen-Activated Protein Kinase Kinases/metabolism
MH  - Mitogen-Activated Protein Kinases/*metabolism
MH  - Monocytes/cytology/drug effects/metabolism
MH  - NF-kappa B/*antagonists & inhibitors
MH  - Phosphorylation
MH  - Protein-Tyrosine Kinases/metabolism
MH  - Sesquiterpenes/*pharmacology
MH  - Tumor Necrosis Factor-alpha/metabolism/*pharmacology
MH  - Up-Regulation/drug effects
MH  - p38 Mitogen-Activated Protein Kinases
MH  - CD83 Antigen
EDAT- 2002/08/10 10:00
MHDA- 2002/09/21 10:01
CRDT- 2002/08/10 10:00
PHST- 2002/08/10 10:00 [pubmed]
PHST- 2002/09/21 10:01 [medline]
PHST- 2002/08/10 10:00 [entrez]
AID - S0091674902000908 [pii]
AID - 10.1067/mai.2002.126381 [doi]
PST - ppublish
SO  - J Allergy Clin Immunol. 2002 Aug;110(2):269-76. doi: 10.1067/mai.2002.126381.