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

• Published in: Journal of neuroimmunology 2010-10, Vol.227 (1), p.52-59
• Main Authors: Caruso, Carla, Sanchez, Mónica, Durand, Daniela, de la Cruz Perez, María, Gonzalez, Patricia V, Lasaga, Mercedes, Scimonelli, Teresa N
• Format: Article
• Language: English
• Subjects: Allergy and Immunology; alpha-MSH - physiology; Animals; Cells, Cultured; CREB; Female; Gene Expression Regulation - immunology; Hypothalamic neurons; Hypothalamus - cytology; Hypothalamus - immunology; Hypothalamus - metabolism; IL-1β; Interferon-gamma - antagonists & inhibitors; Interferon-gamma - biosynthesis; Interferon-gamma - genetics; Lipopolysaccharides - antagonists & inhibitors; Lipopolysaccharides - physiology; Neurodegenerative Diseases - immunology; Neurodegenerative Diseases - metabolism; Neurodegenerative Diseases - pathology; Neurology; Neurons - immunology; Neurons - metabolism; Neurons - pathology; NF-κB; Rats; Rats, Wistar; Receptors, Tumor Necrosis Factor, Type I - biosynthesis; Receptors, Tumor Necrosis Factor, Type I - genetics; TNF-α; Tumor Necrosis Factor-alpha - antagonists & inhibitors; Tumor Necrosis Factor-alpha - biosynthesis; Tumor Necrosis Factor-alpha - genetics; α-MSH
• ISSN: 0165-5728; 1872-8421
• DOI: 10.1016/j.jneuroim.2010.06.013

Abstract 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 24 h 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.