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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
10
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pubmed:dateCreated |
2000-5-25
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pubmed:abstractText |
Tumor necrosis factor-alpha (TNF-alpha) production accompanies CNS insults of all kinds. Because the neuropeptide vasoactive intestinal peptide (VIP) and the structurally related peptide pituitary adenylyl cyclase-activating polypeptide (PACAP) have potent anti-inflammatory effects in the periphery, we investigated whether these effects extend to the CNS. TNF-alpha mRNA was induced within 2 hr after rat spinal cord transection, and its upregulation was suppressed by a synthetic VIP receptor agonist. Cultured rat microglia were used to examine the mechanisms underlying this inhibition because microglia are the likely source of TNF-alpha in injured CNS. In culture, increases in TNF-alpha mRNA resulting from lipopolysaccharide (LPS) stimulation were reduced significantly by 10(-7) m VIP and completely eliminated by PACAP at the same concentration. TNF-alpha protein levels were reduced 90% by VIP or PACAP at 10(-7) m. An antagonist of VPAC(1) receptors blocked the action of VIP and PACAP, and a PAC(1) antagonist blocked the action of PACAP. A direct demonstration of VIP binding on microglia and the existence of mRNAs for VPAC(1) and PAC(1) (but not VPAC(2)) receptors argue for a receptor-mediated effect. The action of VIP is cAMP-mediated because (1) activation of cAMP by forskolin mimics the action; (2) PKA inhibition by H89 reverses the neuropeptide-induced inhibition; and (3) the lipophilic neuropeptide mimic, stearyl-norleucine(17) VIP (SNV), which does not use a cAMP-mediated pathway, fails to duplicate the inhibition. We conclude that VIP and PACAP inhibit the production of TNF-alpha from activated microglia by a cAMP-dependent pathway.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Adcyap1 protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclic AMP,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclic AMP-Dependent Protein Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Forskolin,
http://linkedlifedata.com/resource/pubmed/chemical/Isoquinolines,
http://linkedlifedata.com/resource/pubmed/chemical/Lipopolysaccharides,
http://linkedlifedata.com/resource/pubmed/chemical/N-(2-(4-bromocinnamylamino)ethyl)-5-...,
http://linkedlifedata.com/resource/pubmed/chemical/Neuropeptides,
http://linkedlifedata.com/resource/pubmed/chemical/Pituitary Adenylate...,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Pituitary Adenylate...,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Pituitary Hormone,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Vasoactive Intestinal...,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Vasoactive Intestinal...,
http://linkedlifedata.com/resource/pubmed/chemical/Sulfonamides,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Necrosis Factor-alpha,
http://linkedlifedata.com/resource/pubmed/chemical/Vasoactive Intestinal Peptide
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pubmed:status |
MEDLINE
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pubmed:month |
May
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pubmed:issn |
1529-2401
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pubmed:author |
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pubmed:issnType |
Electronic
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pubmed:day |
15
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pubmed:volume |
20
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
3622-30
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pubmed:dateRevised |
2010-11-18
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pubmed:meshHeading |
pubmed-meshheading:10804204-Animals,
pubmed-meshheading:10804204-Cells, Cultured,
pubmed-meshheading:10804204-Cyclic AMP,
pubmed-meshheading:10804204-Cyclic AMP-Dependent Protein Kinases,
pubmed-meshheading:10804204-Enzyme Inhibitors,
pubmed-meshheading:10804204-Forskolin,
pubmed-meshheading:10804204-Gene Expression,
pubmed-meshheading:10804204-Isoquinolines,
pubmed-meshheading:10804204-Lipopolysaccharides,
pubmed-meshheading:10804204-Microglia,
pubmed-meshheading:10804204-Neurons,
pubmed-meshheading:10804204-Neuropeptides,
pubmed-meshheading:10804204-Pituitary Adenylate Cyclase-Activating Polypeptide,
pubmed-meshheading:10804204-RNA, Messenger,
pubmed-meshheading:10804204-Rats,
pubmed-meshheading:10804204-Rats, Sprague-Dawley,
pubmed-meshheading:10804204-Receptors, Pituitary Adenylate Cyclase-Activating...,
pubmed-meshheading:10804204-Receptors, Pituitary Hormone,
pubmed-meshheading:10804204-Receptors, Vasoactive Intestinal Peptide,
pubmed-meshheading:10804204-Receptors, Vasoactive Intestinal Polypeptide, Type I,
pubmed-meshheading:10804204-Signal Transduction,
pubmed-meshheading:10804204-Spinal Cord Injuries,
pubmed-meshheading:10804204-Sulfonamides,
pubmed-meshheading:10804204-Tumor Necrosis Factor-alpha,
pubmed-meshheading:10804204-Vasoactive Intestinal Peptide
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pubmed:year |
2000
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pubmed:articleTitle |
Vasoactive intestinal peptide and pituitary adenylyl cyclase-activating polypeptide inhibit tumor necrosis factor-alpha production in injured spinal cord and in activated microglia via a cAMP-dependent pathway.
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pubmed:affiliation |
Department of Biological Sciences, Rutgers University, Newark, New Jersey 07102, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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