PMID- 17513725
OWN - NLM
STAT- MEDLINE
DCOM- 20070712
LR  - 20190516
IS  - 0022-1767 (Print)
IS  - 0022-1767 (Linking)
VI  - 178
IP  - 11
DP  - 2007 Jun 1
TI  - Distinct roles of different NF-kappa B subunits in regulating inflammatory and T 
      cell stimulatory gene expression in dendritic cells.
PG  - 6777-88
AB  - TLRs play a critical role in inducing inflammatory and immune responses against 
      microbial agents. In this study, we have investigated the role of NF-kappaB 
      transcription factors in regulating TLR-induced gene expression in dendritic 
      cells, a key APC type. The p50 and cRel NF-kappaB subunits were found to be 
      crucial for regulating genes important for dendritic cell-induced T cell 
      responses (e.g., CD40, IL-12, and IL-18) but not for genes encoding inflammatory 
      cytokines (e.g., TNF-alpha, IL-1alpha, and IL-6). In striking contrast, the RelA 
      subunit was crucial for expression of inflammatory cytokine genes but not T cell 
      stimulatory genes. These novel findings reveal a fundamentally important 
      difference in biological function of genes regulated by different NF-kappaB 
      subunits. Focusing on RelA target gene specificity mechanisms, we investigated 
      whether the kappaB site and/or the unique composition of RelA played the most 
      crucial role. Surprisingly, studies of IL-6 expression showed that the kappaB 
      site is not a primary determinant of RelA target gene specificity. Instead, a 
      major specificity mechanism is the unique ability of RelA to interact with the 
      transcriptional coactivator CREB-binding protein, a function not shared with the 
      closely related cRel subunit. Together, our findings indicate novel and 
      critically important overall roles of NF-kappaB in TLR-induced gene expression 
      that are mediated by unique functions of distinct subunits.
FAU - Wang, Junmei
AU  - Wang J
AD  - Department of Interdisciplinary Oncology, H. Lee Moffitt Cancer Center and 
      Research Institute, University of South Florida, Tampa, FL 33612, USA.
FAU - Wang, Xingyu
AU  - Wang X
FAU - Hussain, Sofia
AU  - Hussain S
FAU - Zheng, Ye
AU  - Zheng Y
FAU - Sanjabi, Shomyseh
AU  - Sanjabi S
FAU - Ouaaz, Fatah
AU  - Ouaaz F
FAU - Beg, Amer A
AU  - Beg AA
LA  - eng
GR  - R01 AI059715/AI/NIAID NIH HHS/United States
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Immunol
JT  - Journal of immunology (Baltimore, Md. : 1950)
JID - 2985117R
RN  - 0 (Cytokines)
RN  - 0 (Inflammation Mediators)
RN  - 0 (NF-kappa B)
RN  - 0 (Protein Subunits)
RN  - 0 (Toll-Like Receptors)
SB  - IM
MH  - Animals
MH  - Cell Line
MH  - Cell Line, Transformed
MH  - Cells, Cultured
MH  - Cytokines/biosynthesis/genetics/physiology
MH  - Dendritic Cells/immunology/metabolism
MH  - Gene Expression Regulation/*immunology
MH  - Humans
MH  - Inflammation Mediators/metabolism/*physiology
MH  - Lymphocyte Activation/*genetics
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - NF-kappa B/*physiology
MH  - Protein Subunits/*physiology
MH  - T-Lymphocyte Subsets/immunology/*metabolism/pathology
MH  - Toll-Like Receptors/physiology
EDAT- 2007/05/22 09:00
MHDA- 2007/07/13 09:00
CRDT- 2007/05/22 09:00
PHST- 2007/05/22 09:00 [pubmed]
PHST- 2007/07/13 09:00 [medline]
PHST- 2007/05/22 09:00 [entrez]
AID - 178/11/6777 [pii]
AID - 10.4049/jimmunol.178.11.6777 [doi]
PST - ppublish
SO  - J Immunol. 2007 Jun 1;178(11):6777-88. doi: 10.4049/jimmunol.178.11.6777.