PMID- 10570261
OWN - NLM
STAT- MEDLINE
DCOM- 19991220
LR  - 20171116
IS  - 0022-1767 (Print)
IS  - 0022-1767 (Linking)
VI  - 163
IP  - 11
DP  - 1999 Dec 1
TI  - Differential role for p38 mitogen-activated protein kinase in regulating 
      CD40-induced gene expression in dendritic cells and B cells.
PG  - 5786-95
AB  - We investigated whether human monocyte-derived dendritic cells (DCs) differed 
      from tonsillar B cells in the set of cell fate genes they express constitutively 
      and in the way these genes are affected after CD40 ligation. In particular, 
      Bcl-2, TNF receptor-associated factor-2 (TRAF2), and TRAF4 were clearly inducible 
      via CD40 in B cells but not in DCs. DCs, unlike B cells, were induced to increase 
      expression of IL-1beta, IL-1Ra, IL-8, IL-12 p40, RANTES, macrophage inflammatory 
      protein-1alpha, and monocyte chemoattractant protein-1 after CD40 ligation. We 
      next tested whether CD40-induced signaling pathways were different in DCs vs B 
      cells. In DCs, as in B cells, CD40 ligation activated p38 mitogen-activated 
      protein kinase (MAPK), its downstream target, MAPKAPK-2, and the c-Jun N-terminal 
      kinase. The p38 MAPK-specific inhibitor, SB203580, blocked CD40-induced MAPKAPK-2 
      activation, but did not affect activation of c-Jun N-terminal kinase. 
      Furthermore, unlike in B cells, extracellular signal-regulated kinase-1 and -2 
      were activated after CD40 ligation in DCs. SB203580 strongly blocked CD40-induced 
      IL-12 p40 production in DCs at both mRNA and protein levels, while having minimal 
      effect on CD40-induced expression of the chemokine RANTES. In contrast, no 
      detectable IL-12 p40 protein was secreted in CD40-stimulated B cells. 
      Furthermore, CD40-induced mRNA expression of cellular inhibitor of apoptosis 
      protein-2 was also dependent on the p38 MAPK pathway in DCs and differed compared 
      with that in B cells. In conclusion, CD40 induces distinct programs in DCs and B 
      cells, and the set of p38 MAPK-dependent genes in DCs (IL-12 p40 and cellular 
      inhibitor of apoptosis protein-2) is different from that in B cells (IL-10 and 
      IL-1beta).
FAU - Aicher, A
AU  - Aicher A
AD  - Department of Microbiology, University of Washington, Seattle, WA 98195, USA.
FAU - Shu, G L
AU  - Shu GL
FAU - Magaletti, D
AU  - Magaletti D
FAU - Mulvania, T
AU  - Mulvania T
FAU - Pezzutto, A
AU  - Pezzutto A
FAU - Craxton, A
AU  - Craxton A
FAU - Clark, E A
AU  - Clark EA
LA  - eng
GR  - GM37905/GM/NIGMS NIH HHS/United States
GR  - RR00166/RR/NCRR NIH HHS/United States
PT  - Comparative Study
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 (CD40 Antigens)
RN  - 0 (Chemokines)
RN  - 0 (Cytokines)
RN  - 0 (Inhibitor of Apoptosis Proteins)
RN  - 0 (Proteins)
RN  - 0 (Proto-Oncogene Proteins c-bcl-2)
RN  - 0 (TNF Receptor-Associated Factor 1)
RN  - 0 (TNF Receptor-Associated Factor 3)
RN  - 0 (TNF Receptor-Associated Factor 4)
RN  - 0 (TRAF4 protein, human)
RN  - 0 (Tumor Necrosis Factor Receptor-Associated Peptides and Proteins)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
RN  - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
SB  - IM
MH  - Apoptosis
MH  - B-Lymphocytes/*immunology
MH  - CD40 Antigens/*metabolism
MH  - Chemokines/biosynthesis
MH  - Cytokines/biosynthesis
MH  - Dendritic Cells/*immunology
MH  - Gene Expression Regulation
MH  - Humans
MH  - Immunologic Capping
MH  - Inhibitor of Apoptosis Proteins
MH  - Mitogen-Activated Protein Kinases/*metabolism
MH  - Monocytes/immunology
MH  - Palatine Tonsil/cytology/immunology
MH  - Protein Biosynthesis
MH  - *Proteins
MH  - Proto-Oncogene Proteins c-bcl-2/biosynthesis
MH  - Signal Transduction
MH  - TNF Receptor-Associated Factor 1
MH  - TNF Receptor-Associated Factor 3
MH  - TNF Receptor-Associated Factor 4
MH  - Tumor Necrosis Factor Receptor-Associated Peptides and Proteins
MH  - p38 Mitogen-Activated Protein Kinases
EDAT- 1999/11/26 00:00
MHDA- 1999/11/26 00:01
CRDT- 1999/11/26 00:00
PHST- 1999/11/26 00:00 [pubmed]
PHST- 1999/11/26 00:01 [medline]
PHST- 1999/11/26 00:00 [entrez]
AID - ji_v163n11p5786 [pii]
PST - ppublish
SO  - J Immunol. 1999 Dec 1;163(11):5786-95.