Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
8
pubmed:dateCreated
2011-4-5
pubmed:abstractText
This study evaluates the ability of a novel TLR7 ligand (9-benzyl-2-butoxy-8-hydroxy adenine, called SA-2) to affect IL-17 response. The SA-2 activity on the expression of IL-17A and IL-17-related molecules was evaluated in acute and chronic models of asthma as well as in in vivo and in vitro ?-galactosyl ceramide (?-GalCer)-driven systems. SA-2 prepriming reduced neutrophils in bronchoalveolar lavage fluid and decreased methacoline-induced airway hyperresponsiveness in murine asthma models. These results were associated with the reduction of IL-17A (and type 2 cytokines) as well as of molecules favoring Th17 (and Th2) development in lung tissue. The IL-17A production in response to ?-GalCer by spleen mononuclear cells was inhibited in vitro by the presence of SA-2. Reduced IL-17A (as well as IFN-? and IL-13) serum levels in mice treated with ?-GalCer plus SA-2 were also observed. The in vitro results indicated that IL-10 produced by B cells and IL-10-promoting molecules such as IFN-? and IL-27 by dendritic cells are the major player for SA-2-driven IL-17A (and also IFN-? and IL-13) inhibition. The in vivo experiments with anti-cytokine receptor Abs provided evidence of an early IL-17A inhibition essentially due to IL-10 produced by resident peritoneal cells and of a delayed IL-17A inhibition sustained by IFN-? and IL-27, which in turn drive effector T cells to IL-10 production. These findings suggest that such TLR7 agonist downregulating Th17 (as well as Th2) response has to be considered a valid candidate for novel vaccine formulations in allergy.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
1550-6606
pubmed:author
pubmed:issnType
Electronic
pubmed:day
15
pubmed:volume
186
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
4707-15
pubmed:meshHeading
pubmed-meshheading:21389257-Adenine, pubmed-meshheading:21389257-Animals, pubmed-meshheading:21389257-Asthma, pubmed-meshheading:21389257-B-Lymphocytes, pubmed-meshheading:21389257-Cells, Cultured, pubmed-meshheading:21389257-Cytokines, pubmed-meshheading:21389257-Dendritic Cells, pubmed-meshheading:21389257-Enzyme-Linked Immunosorbent Assay, pubmed-meshheading:21389257-Female, pubmed-meshheading:21389257-Galactosylceramides, pubmed-meshheading:21389257-Gene Expression, pubmed-meshheading:21389257-Injections, Intraperitoneal, pubmed-meshheading:21389257-Interferon-gamma, pubmed-meshheading:21389257-Interleukin-10, pubmed-meshheading:21389257-Interleukin-13, pubmed-meshheading:21389257-Interleukin-17, pubmed-meshheading:21389257-Leukocytes, Mononuclear, pubmed-meshheading:21389257-Lung, pubmed-meshheading:21389257-Mice, pubmed-meshheading:21389257-Mice, Inbred C57BL, pubmed-meshheading:21389257-Reverse Transcriptase Polymerase Chain Reaction, pubmed-meshheading:21389257-T-Lymphocytes, pubmed-meshheading:21389257-Th17 Cells, pubmed-meshheading:21389257-Th2 Cells, pubmed-meshheading:21389257-Toll-Like Receptor 7
pubmed:year
2011
pubmed:articleTitle
The TLR7 ligand 9-benzyl-2-butoxy-8-hydroxy adenine inhibits IL-17 response by eliciting IL-10 and IL-10-inducing cytokines.
pubmed:affiliation
Immunoallergology Unit, Careggi Hospital, 50134 Florence, Italy.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't