Effect of NDP-α-MSH on PPAR-γ and –β Expression and Anti-Inflammatory Cytokine Release in Rat Astrocytes and Microglia

Carniglia, Lila; Durand, Daniela; Caruso, Carla; Lasaga, Mercedes
February 2013
PLoS ONE;Feb2013, Vol. 8 Issue 2, p1
Academic Journal
Brain inflammation plays a central role in numerous brain pathologies. Microglia and astrocytes are the main effector cells that become activated when an inflammatory process takes place within the central nervous system. α-melanocyte-stimulating hormone (α-MSH) is a neuropeptide with proven anti-inflammatory properties. It binds with highest affinity to the melanocortin receptor 4 (MC4R), which is present in astrocytes and upon activation triggers anti-inflammatory pathways. The aim of this research was to identify anti-inflammatory mediators that may participate in the immunomodulatory effects of melanocortins in glial cells. Since peroxisome proliferator-activated receptors (PPARs) have recently been implicated in the modulation of inflammation, we investigated the effect of an α-MSH analog, [Nle4, D-Phe7]-α-MSH (NDP-α-MSH), on PPAR-β and PPAR-γ gene and protein expression in rat primary astrocytes and microglia. We initially demonstrated that rat primary microglia express MC4R and showed that treatment with NDP-α-MSH increases PPAR-γ protein levels and strongly decreases PPAR-β levels in both astrocytes and microglia. We also showed that extracellular signal-regulated kinase 1/2 (ERK1/2)–mediated signaling is partially involved in these effects in a cell-specific fashion. Finally, we showed that NDP-α-MSH stimulates the release of the anti-inflammatory cytokines IL-10 and TGF-β from microglia and astrocytes, respectively. The presented data suggest a role for IL-10 and TGF-β in the protective action of melanocortins and a connection between MC4R pathway and that of the nuclear receptor PPAR-γ. This is the first report providing evidence that MC4R is expressed in rat primary microglia and that melanocortins modulate PPAR levels in glial cells. Our findings provide new insights into the mechanisms underlying the activation of glial MC4R and open perspectives for new therapeutic strategies for the treatment of inflammation-mediated brain diseases.


Related Articles

  • Altered expression of pro- and anti-inflammatory cytokines is associated with reduced cardiac function in rats following coronary microembolization. Li, Lang; Zhao, Xianming; Lu, Yongguang; Huang, Weiqiang; Wen, Weiming // Molecular & Cellular Biochemistry;Sep2010, Vol. 342 Issue 1/2, p183 

    Coronary microembolization (CME) is a spontaneous event in patients with ischemic heart disease and a potential iatrogenic complication in patients undergoing coronary interventions. CME induces an obvious inflammatory reaction, characterized by cellular infiltration, particularly of...

  • Curcumin Protects Dopaminergic Neuron Against LPS Induced Neurotoxicity in Primary Rat Neuron/Glia Culture. Sufen Yang; Dan Zhang; Zhengqin Yang; Xiaoming Hu; Steven Qian; Jie Liu; Belinda Wilson; Michelle Block; Jau-Shyong Hong // Neurochemical Research;Oct2008, Vol. 33 Issue 10, p2044 

    Abstract  Using primary rat mesencephalic neuron-glia cultures as an in vitro model of Parkinson’s disease (PD), we tested the effect of curcumin, a natural dietary pigment with well-known anti-inflammation effects, on dopaminergic (DA) degeneration. Curcumin...

  • Anti-Inflammatory Effects of Total Isoflavones from Pueraria lobata on Cerebral Ischemia in Rats. Dong Wook Lim; Changho Lee; In-Ho Kim; Yun Tai Kim // Molecules;Sep2013, Vol. 18 Issue 9, p10404 

    Puerariae radix, the dried root of Pueraria lobata Ohwi, is one of earliest and most important edible crude herbs used for various medical purposes in Oriental medicine. The aim of the present study was to determine the anti-inflammatory effects of Total Isoflavones from P. lobata (TIPL), which...

  • Anti-Inflammatory Activity of Salvadora persica L. against Carrageenan Induced Paw Oedema in Rat Relevant to Inflammatory Cytokines. Ibrahim, Abeer Y.; El-Gengaihi, Souad E.; Motawea, Hemaia M.; Sleem, Amany M. // Notulae Scientia Biologicae;2011, Vol. 3 Issue 4, p22 

    In this study, the anti-inflammatory effect of aqueous alcoholic crude extract and ethyl acetate extract of miswak sticks (Salvadora persica L.) was investigated in carrageenan induced rat paw oedema in respect to immunological parameters. Adult male sapargue dawely rats were classified into...

  • Cytokine Profile of Peripheral Blood in Rats with Various Behavioral Characteristics during Acute Emotional Stress. Kalinichenko, L.; Koplik, E.; Pertsov, S. // Bulletin of Experimental Biology & Medicine;Feb2014, Vol. 156 Issue 4, p441 

    The cytokine profile of peripheral blood plasma was studied in rats with various behavioral characteristics after acute emotional stress (1-hour immobilization with simultaneous electrocutaneous stimulation). Under basal conditions the concentrations of pro-inflammatory (IL-1α, IL-1β,...

  • Memory Disorders in Rats after Impairment of the Dorsal Hippocampal CA3 Field with Kainic Acid. Gordon, R.; Kapralova, M.; Godukhin, O.; Arkhipov, V. // Bulletin of Experimental Biology & Medicine;Oct2013, Vol. 155 Issue 6, p805 

    We studied the possibility of conditioning of food-procuring response in animals after impairment of the dorsal hippocampal region with kainic acid. Histological studies of brain sections showed that the greater part of dorsal hippocampal CA3 pyramidal neurons were lyzed in 2 weeks after kainic...

  • Short-chain fatty acids act as antiinflammatory mediators by regulating prostaglandin E2 and cytokines. Cox, Mary Ann; Jackson, James; Stanton, Michaela; Rojas-Triana, Alberto; Bober, Loretta; Laverty, Maureen; Xiaoxin Yang; Feng Zhu; Jianjun Liu; Suke Wang; Monsma, Frederick; Vassileva, Galya; Maguire, Maureen; Gustafson, Eric; Bayne, Marvin; Chuan-Chu Chou; Lundell, Daniel; Chung-Her Jenh; Wei Tang; Dae-Yeul Yu // World Journal of Gastroenterology;11/28/2009, Vol. 15 Issue 44, p5549 

    AIM: To investigate the effect of short-chain fatty acids (SCFAs) on production of prostaglandin E2(PGE2), cytokines and chemokines in human monocytes. METHODS: Human neutrophils and monocytes were isolated from human whole blood by using 1-Step Polymorph and RosetteSep Human Monocyte Enrichment...

  • Effects of Sub-Acute Exposure to Rhodium (as Rh (III) chloride hydrate) on Cytokines in Female Wistar Rats. Iavicoli, Ivo; Sgambato, Alessandro; Fontana, Luca; Marinaccio, Alessandro; Leso, Veruscka; Corbi, Maddalena; Bergamaschi, Antonio; Calabrese, Edward // Bulletin of Environmental Contamination & Toxicology;Sep2012, Vol. 89 Issue 3, p686 

    Quantitative changes in different cytokines were determined in serum of female Wistar rats exposed to Rhodium (III) chloride hydrate to evaluate its early effects on the immune system. Findings revealed an inhibitory effect of Rh salt since each cytokine, with the exceptions of IL-1α and IL-2...

  • A novel fluorinated stilbene exerts hepatoprotective properties in CCl4-induced acute liver damage. Rivera, Horacio; Morales-R�os, Martha S.; Bautista, Wendy; Shibayama, Mineko; Tsutsumi, V�ctor; Muriel, Pablo; P�rez-�lvarez, V�ctor // Canadian Journal of Physiology & Pharmacology;Oct2011, Vol. 89 Issue 10, p759 

    There has been a recently increase in the development of novel stilbene-based compounds with in vitro anti-inflamatory properties. For this study, we synthesized and evaluated the anti-inflammatory properties of 2 fluorinated stilbenes on carbon tetrachloride (CCl4)-induced acute liver damage....


Read the Article


Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics