6533b853fe1ef96bd12acb62
RESEARCH PRODUCT
Beta-MSH inhibits brain inflammation via MC(3)/(4) receptors and impaired NF-kappaB signaling.
Olga KirjanovaLiga ZvejnieceMaija DambrovaReinis VilskerstsLarisa BaumaneValentina GordjusinaJarl E. S. WikbergEdgars LiepinshRuta MucenieceLiga KrigereIvars Kalvinshsubject
LipopolysaccharidesMalemedicine.medical_specialtyImmunologyNitric Oxide Synthase Type IIInflammationElectrophoretic Mobility Shift AssayNitric OxidePeptides CyclicNitric oxidechemistry.chemical_compoundMiceInternal medicinebeta-MSHmedicineImmunology and AllergyAnimalsDrug InteractionsReceptorBrain ChemistryMice Inbred ICRbiologyDose-Response Relationship DrugImmunochemistryElectron Spin Resonance SpectroscopyNF-kappa BNF-κBHormonesCell biologyNitric oxide synthaseDisease Models AnimalEndocrinologyNeurologyMechanism of actionchemistrybiology.proteinEncephalitisReceptor Melanocortin Type 4Neurology (clinical)medicine.symptomMelanocortinSignal transductionhormones hormone substitutes and hormone antagonistsReceptor Melanocortin Type 3Signal Transductiondescription
The anti-inflammatory effects of melanocortin peptides have been demonstrated in different inflammation models. This is the first report describing the molecular mechanisms for the beta-MSH-induced suppression of bacterial lipopolisaccharide (LPS)-caused brain inflammation. We found that beta-MSH suppresses LPS-induced nuclear translocation of the transcription factor NF-kappaB, and inhibits the expression of inducible nitric oxide synthase, and the following nitric oxide overproduction in the brain, in vivo. Moreover, administering the preferentially MC(4) receptor selective antagonist HS014 blocked completely these effects, suggesting a tentative MC(4) receptor mediated mechanism of action for the beta-MSH. However, as HS014 shows quite low selectivity vis-a-vis the MC(3) receptor, a role for the MC(3) receptor cannot be excluded. In conclusion, our results show that beta-MSH is capable of inhibiting brain inflammation via activation of melanocortin receptors, of the subtypes 4 and/or 3.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2005-12-01 | Journal of neuroimmunology |