PMID- 10804204
OWN - NLM
STAT- MEDLINE
DCOM- 20000525
LR  - 20231014
IS  - 1529-2401 (Electronic)
IS  - 0270-6474 (Print)
IS  - 0270-6474 (Linking)
VI  - 20
IP  - 10
DP  - 2000 May 15
TI  - 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.
PG  - 3622-30
AB  - 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.
FAU - Kim, W K
AU  - Kim WK
AD  - Department of Biological Sciences, Rutgers University, Newark, New Jersey 07102, 
      USA.
FAU - Kan, Y
AU  - Kan Y
FAU - Ganea, D
AU  - Ganea D
FAU - Hart, R P
AU  - Hart RP
FAU - Gozes, I
AU  - Gozes I
FAU - Jonakait, G M
AU  - Jonakait GM
LA  - eng
GR  - AI 41786-02/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Neurosci
JT  - The Journal of neuroscience : the official journal of the Society for 
      Neuroscience
JID - 8102140
RN  - 0 (Adcyap1 protein, rat)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Isoquinolines)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Neuropeptides)
RN  - 0 (Pituitary Adenylate Cyclase-Activating Polypeptide)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide)
RN  - 0 (Receptors, Pituitary Hormone)
RN  - 0 (Receptors, Vasoactive Intestinal Peptide)
RN  - 0 (Receptors, Vasoactive Intestinal Polypeptide, Type I)
RN  - 0 (Sulfonamides)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 1F7A44V6OU (Colforsin)
RN  - 37221-79-7 (Vasoactive Intestinal Peptide)
RN  - E0399OZS9N (Cyclic AMP)
RN  - EC 2.7.11.11 (Cyclic AMP-Dependent Protein Kinases)
RN  - M876330O56 (N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide)
SB  - IM
MH  - Animals
MH  - Cells, Cultured
MH  - Colforsin/pharmacology
MH  - Cyclic AMP/*metabolism
MH  - Cyclic AMP-Dependent Protein Kinases/metabolism
MH  - Enzyme Inhibitors/pharmacology
MH  - Gene Expression/drug effects
MH  - Isoquinolines/pharmacology
MH  - Lipopolysaccharides/pharmacology
MH  - Microglia/cytology/drug effects/*enzymology
MH  - Neurons/cytology
MH  - Neuropeptides/*pharmacology
MH  - Pituitary Adenylate Cyclase-Activating Polypeptide
MH  - RNA, Messenger/metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide
MH  - Receptors, Pituitary Hormone/genetics
MH  - Receptors, Vasoactive Intestinal Peptide/agonists/genetics
MH  - Receptors, Vasoactive Intestinal Polypeptide, Type I
MH  - Signal Transduction/physiology
MH  - Spinal Cord Injuries/drug therapy/*metabolism/pathology
MH  - *Sulfonamides
MH  - Tumor Necrosis Factor-alpha/*genetics
MH  - Vasoactive Intestinal Peptide/*pharmacology
PMC - PMC6772690
EDAT- 2000/05/11 00:00
MHDA- 2000/06/08 00:00
PMCR- 2000/11/15
CRDT- 2000/05/11 00:00
PHST- 2000/05/11 00:00 [pubmed]
PHST- 2000/06/08 00:00 [medline]
PHST- 2000/05/11 00:00 [entrez]
PHST- 2000/11/15 00:00 [pmc-release]
AID - 20/10/3622 [pii]
AID - 4149 [pii]
AID - 10.1523/JNEUROSCI.20-10-03622.2000 [doi]
PST - ppublish
SO  - J Neurosci. 2000 May 15;20(10):3622-30. doi: 10.1523/JNEUROSCI.20-10-03622.2000.