Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2009-4-1
pubmed:abstractText
Dendritic cells (DCs) play an important role in bridging innate and adaptive immunity. These APCs have the ability to recognize specific molecular signatures of pathogens through TLRs. In particular, the intracellular TLR7 and TLR8, mediating the recognition of ssRNA by DCs, play a major role in the immune response during viral infection. Although differences have been identified between TLR7 and TLR8, in terms of cellular expression and functions, the signaling pathways that lead to DC maturation following TLR7 or TLR8 engagement are largely unknown. We compared the signaling pathways involved in human CD34-DC maturation induced by agonists selective for TLR7 (imiquimod) or TLR8 (3M002). TLR7 and TLR8 activation up-regulated CCR7, CD40, CD86, and CD83 expression and IL-6 and IL-12p40 production. However, only TLR8 activation led to IL-12p70 production and il-12p35 mRNA expression. We found that upon TLR7 and TLR8 activation, JNK and NF-kappaB positively regulated the expression of CCR7, CD86, CD83, and CD40 and the production of IL-6 and IL-12p40. However, although p38MAPK participated in the up-regulation of maturation markers in response to TLR7 activation, this kinase exerted an inhibitory effect on CD40 expression and IL-12 production in TLR8-stimulated DCs. We also showed that the Jak/STAT signaling pathway was involved in CD40 expression and cytokine production in TLR7-stimulated DCs but negatively regulated CD83 expression and cytokine secretion in DCs activated through TLR8. This study showed that TLR7 and TLR8 activate similar signaling pathways that play different roles in DC maturation, depending on which TLR is triggered.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
1938-3673
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
85
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
673-83
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed:year
2009
pubmed:articleTitle
TLR7 and TLR8 agonists trigger different signaling pathways for human dendritic cell maturation.
pubmed:affiliation
Université Paris-Sud 11, INSERM UMR-S 749, Faculté de Pharmacie, 92296 Châtenay-Malabry, France.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't