Linked Life Data

12816950

Source:http://linkedlifedata.com/resource/pubmed/id/12816950

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
35
pubmed:dateCreated
2003-8-25
pubmed:abstractText
The neuropeptide alpha-melanocyte-stimulating hormone (alpha-MSH) inhibits inflammation by down-regulating the expression of proinflammatory cytokines such as tumor necrosis factor-alpha (TNF-alpha) in leukocytes via stimulation of alpha-MSH cell surface receptors. However, the signaling mechanism of alpha-MSH action has not yet been clearly elucidated. Here, we have investigated signaling pathways by which alpha-MSH inhibits lipopolysaccharide (LPS)-induced TNF-alpha production in leukocytes such as THP-1 cells. We focused on the possible roles of protein kinase A (PKA), p38 kinase, and nuclear factor kappa B (NF kappa B) signaling. In THP-1 cells, LPS is known to activate p38 kinase, which in turn activates NF kappa B to induce TNF-alpha production. We found that pretreatment of cells with alpha-MSH blocked LPS-induced p38 kinase and NF kappa B activation as well as TNF-alpha production. This response was proportional to alpha-MSH receptor expression levels, and addition of an alpha-MSH receptor antagonist abolished the inhibitory effects. In addition, alpha-MSH treatment activated PKA, and PKA inhibition abrogated the inhibitory effects of alpha-MSH on p38 kinase activation, NF kappa B activation, and TNF-alpha production. Taken together, our results indicate that stimulation of PKA by alpha-MSH causes inhibition of LPS-induced activation of p38 kinase and NF kappa B to block TNF-alpha production.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
29
pubmed:volume
278
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
32914-20
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:12816950-Blotting, Western, pubmed-meshheading:12816950-Cyclic AMP-Dependent Protein Kinases, pubmed-meshheading:12816950-Enzyme Activation, pubmed-meshheading:12816950-Enzyme Inhibitors, pubmed-meshheading:12816950-HL-60 Cells, pubmed-meshheading:12816950-Humans, pubmed-meshheading:12816950-Leukocytes, pubmed-meshheading:12816950-Lipopolysaccharides, pubmed-meshheading:12816950-Luciferases, pubmed-meshheading:12816950-Mitogen-Activated Protein Kinases, pubmed-meshheading:12816950-NF-kappa B, pubmed-meshheading:12816950-Precipitin Tests, pubmed-meshheading:12816950-RNA, Messenger, pubmed-meshheading:12816950-Reverse Transcriptase Polymerase Chain Reaction, pubmed-meshheading:12816950-Signal Transduction, pubmed-meshheading:12816950-Time Factors, pubmed-meshheading:12816950-Tumor Necrosis Factor-alpha, pubmed-meshheading:12816950-alpha-MSH, pubmed-meshheading:12816950-p38 Mitogen-Activated Protein Kinases
pubmed:year
2003
pubmed:articleTitle
alpha-Melanocyte-stimulating hormone inhibits lipopolysaccharide-induced tumor necrosis factor-alpha production in leukocytes by modulating protein kinase A, p38 kinase, and nuclear factor kappa B signaling pathways.
pubmed:affiliation
Proteome Research Lab, Korea Research Institute of Bioscience and Biotechnology, Daejon 305-600, Korea.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't