α-melanocyte-stimulating hormone modulates lipopolysaccharide plus interferon-γ-induced tumor necrosis factor-α expression but not tumor necrosis factor-α receptor expression in cultured hypothalamic neurons.
In a previous work we showed that the melanocortin alpha-melanocyte-stimulating hormone (α-MSH) exerts anti-inflammatory action through melanocortin 4 receptor (MC4R) in vivo in rat hypothalamus. In this work, we examined the effect of α-MSH on the expression of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) and their receptors in primary cultured rat hypothalamic neurons. We also investigated α-MSH's possible mechanism/s of action. α-MSH (5 μM) decreased TNF-α expression induced by 24h administration of a combination of bacterial lipopolysaccharide (LPS, 1 μg/ml) plus interferon-γ (IFN-γ, 50 ng/ml). Expression of TNF-α and IL-1β receptors TNFR1, TNFR2 and IL-1RI, was up-regulated by LPS+IFN-γ whereas α-MSH did not modify basal or LPS+IFN-γ-induced-TNFRs or IL-1RI expression. Both α-MSH and LPS+IFN-γ treatments increased CREB activation. α-MSH did not modify NF-κB activation induced by LPS+IFN-γ in hypothalamic neurons. In conclusion, our data show that α-MSH reduces TNF-α expression in hypothalamic neurons by a mechanism which could be mediated by CREB. The regulation of inflammatory processes in the hypothalamus by α-MSH might help to prevent neurodegeneration resulting from inflammation.
Caruso
Carla
C
Instituto de Investigaciones en Reproducción, Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, Argentina. ccaruso@fmed.uba.ar
Sanchez
Mónica
M
Durand
Daniela
D
Perez
María de la Cruz
Mde L
Gonzalez
Patricia V
PV
Lasaga
Mercedes
M
Scimonelli
Teresa N
TN
D000818:Animals; D002478:Cells, Cultured; D005260:Female; D005786:Gene Expression Regulation / Q000276:immunology; D007031:Hypothalamus / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D007371:Interferon-gamma / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000235:genetics; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors / Q000502:physiology*; D019636:Neurodegenerative Diseases / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D009474:Neurons / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000096:biosynthesis / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000235:genetics; D000521:alpha-MSH / Q000502:physiology*
D008070:Lipopolysaccharides; D047888:Receptors, Tumor Necrosis Factor, Type I; D014409:Tumor Necrosis Factor-alpha; D000521:alpha-MSH; D007371:Interferon-gamma