Linked Life Data

21145111

Source:http://linkedlifedata.com/resource/pubmed/id/21145111

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2011-1-3
pubmed:abstractText
Interleukin (IL)-23 is an essential cytokine involved in the expansion of a novel CD4(+) T helper subset known as Th17, which has been implicated in the pathogenesis of periodontitis recently. This study hypothesised that Th17 signature cytokine IL-17 may target specialised human periodontal ligament fibroblasts (hPDLFs) for production of IL-23 p19, a key subunit of IL-23. Primary hPDLFs had steady expression of IL-17 receptor (IL-17R) mRNA and surface-bound protein. IL-17 was capable of stimulating the expression of IL-23 p19 mRNA and protein in cultured hPDLFs, which was attenuated by IL-17 or IL-17R neutralising antibodies. In accordance with the enhanced expression of IL-23 p19, IL-17 stimulation resulted in rapid activation of Akt, p38 mitogen-activated protein kinase (MAPK), extracellular signal-regulated kinase (ERK) 1/2, c-Jun-N-terminal kinase (JNK), nuclear factor-kappaB (NF-?B), and activator protein-1 (AP-1) in hPDLFs. Inhibitors of Akt, p38 MAPK, ERK 1/2, or NF-?B significantly suppressed, whereas blocking JNK and AP-1 substantially augmented IL-23 p19 production from IL-17-stimulated hPDLFs. Moreover, IL-17-initiated NF-?B activation was blocked by Akt, p38 MAPK, or ERK 1/2 inhibition, while AP-1 activity was specifically abrogated by JNK inhibition. Thus, these results provide evidence that hPDLFs are a target of Th17, and that IL-17 appears to up-regulate the expression of IL-23 p19 via a homeostatic mechanism involving Akt-, p38 MAPK-, and ERK 1/2-dependent NF-?B signalling versus the JNK/AP-1 pathway. Taken together, our findings suggest that disruption of the interaction between IL-17 and IL-23 may be a potential therapeutic approach in the treatment of periodontitis.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
1872-9142
pubmed:author
pubmed:copyrightInfo
Crown Copyright © 2010. Published by Elsevier Ltd. All rights reserved.
pubmed:issnType
Electronic
pubmed:volume
48
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
647-56
pubmed:meshHeading
pubmed:year
2011
pubmed:articleTitle
IL-17R activation of human periodontal ligament fibroblasts induces IL-23 p19 production: Differential involvement of NF-?B versus JNK/AP-1 pathways.
pubmed:affiliation
The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) & Key Laboratory of Oral Biomedicine Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan, China.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, Non-U.S. Gov't