Linked Life Data

20943775

Source:http://linkedlifedata.com/resource/pubmed/id/20943775

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2010-12-15
pubmed:abstractText
Despite evidence that smoking confers protection against neurological disorders, how and whether specific nicotinic receptor subtypes are involved is unknown. We reported previously that nicotine suppresses constitutive nuclear factor ?B (NF-?B) activity and thereby proinflammatory cytokine (PIC) production in SHEP1 cells stably transfected with ?4?2 nicotinic receptors. Here, we report the anti-inflammatory effects of nicotine pretreatment in lipopolysaccharide (LPS)-stimulated SHEP1 cells. Nicotine (100-300 nM, concentrations found in smoker's blood) blocked LPS-induced NF-?B translocation and production of PICs interleukin (IL)-1? and IL-6 but only partially blocked inhibitor of nuclear factor-?B? (I?B?) phosphorylation. These effects were exclusively in cells transfected with ?4?2 receptors but not in wild types. The cell-permeable calcium chelator 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid-acetoxymethyl ester, the adenylate cyclase stimulant forskolin, and a specific protein kinase A (PKA) inhibitor PKI 14-22-amide failed to block the effect of nicotine on LPS-induced NF-?B translocation and I?B? phosphorylation. However, the effects of nicotine on NF-?B activity were significantly blocked by the highly specific janus kinase 2 (JAK2) inhibitor ?-cyano-(3,4-dihydroxy)-N-benzylcinnamide (AG-490) and the signal transducer and activator of transcription 3 (STAT3) inhibitor 2-hydroxy-4-[[[[(4-methylphenyl)sulfonyl]oxy]acetyl]amino]-benzoic acid (NSC74859). These findings reveal a calcium- and cAMP-PKA-independent signaling cascade and suggest a role for JAK2-STAT3 transduction in ?4?2-mediated attenuation of LPS-induced inflammation. Anti-inflammatory effects of nicotine may therefore be mediated through ?4?2 receptors, the predominant high-affinity binding sites for nicotine in the central nervous system, in addition to the better-established ?7 receptors.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
1521-0111
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
79
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
167-74
pubmed:meshHeading
pubmed:year
2011
pubmed:articleTitle
?4?2 nicotinic receptors partially mediate anti-inflammatory effects through Janus kinase 2-signal transducer and activator of transcription 3 but not calcium or cAMP signaling.
pubmed:affiliation
Department of Pharmaceutical Science, Northeastern University, Boston, Massachusetts 02115, USA.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, Non-U.S. Gov't