Aicher, A, Shu, GL, Magaletti, D, Mulvania, T, Pezzutto, A, Craxton, A and Clark, EA, 1999. Differential role for p38 mitogen-activated protein kinase in regulating CD40-induced gene expression in dendritic cells and B cells. Journal of Immunology, 163 (11), pp. 5786-5795. ISSN 0022-1767
Full text not available from this repository.Abstract
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-1ß, IL-1Ra, IL-8, IL-12 p40, RANTES, macrophage inflammatory protein-1, 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-1ß).
Item Type: | Journal article |
---|---|
Publication Title: | Journal of Immunology |
Creators: | Aicher, A., Shu, G.L., Magaletti, D., Mulvania, T., Pezzutto, A., Craxton, A. and Clark, E.A. |
Publisher: | American Association of Immunologists |
Date: | 1999 |
Volume: | 163 |
Number: | 11 |
ISSN: | 0022-1767 |
Rights: | Copyright © 1999 by The American Association of Immunologists |
Divisions: | Schools > School of Science and Technology |
Record created by: | EPrints Services |
Date Added: | 09 Oct 2015 10:26 |
Last Modified: | 19 Oct 2015 14:32 |
URI: | https://irep.ntu.ac.uk/id/eprint/13044 |
Actions (login required)
Edit View |
Statistics
Views
Views per month over past year
Downloads
Downloads per month over past year