Data from Alzheimer's disease (AD) patients and AD animal models demonstrate the accumulation of inflammatory microglia at sites of insoluble fibrillar β-amyloid protein (fAβ) deposition. It is known that fAβ binds to CD36, a type B scavenger receptor also involved in internalization of oxidized low-density lipoprotein (LDL), and initiate a signaling cascade that regulates microglial recruitment, activation, and secretion of inflammatory mediators leading to neuronal dysfunction and death. The recent demonstration of a binding site for the growth hormone secretagogues (GHS) on CD36 prompted us to ascertain whether ghrelin and synthetic GHS could modulate the synthesis of inflammatory cytokines in fAβ-activated microglia cells. We demonstrate that N9 microglia cells express the CD36 and are a suitable model to study the activation of inflammatory cytokines synthesis. In fact, in N9 cells exposed to fAβ25-35 for 24 hr, the expression of interleukin (IL)-1β and IL-6 mRNA significantly increased. Interestingly, 10-7 M desacyl-ghrelin, hexarelin, and EP80317 in the nanomolar range effectively counteracted fAβ25-35 stimulation of IL-6 mRNA levels, whereas ghrelin was ineffective. Similarly, the effects of fAβ25-35 on IL-1b mRNA levels were attenuated by desacyl-ghrelin, hexarelin, and EP80317, but not ghrelin. Because we have observed that the specific GHS receptor GHS-R1a is not expressed in N9 cells, the actions of GHS should be mediated by different receptors. Reportedly, hexarelin and EP80317 are capable of binding the CD36 in mouse macrophages and reducing atherosclerotic plaque deposition in mice. We conclude that desacyl-ghrelin, hexarelin, and EP80317 might interfere with fAβ activation of CD36 in microglia cells. © 2009 Wiley-Liss, Inc.

Bulgarelli, I., Tamiazzo, L., Bresciani, E., Rapetti, D., Caporali, S., Lattuada, D., et al. (2009). Desacyl-ghrelin and Synthetic GH-secretagogues Modulate the Production of Inflammatory Cytokines in Mouse Microglia Cells Stimulated by beta-Amyloid Fibrils. JOURNAL OF NEUROSCIENCE RESEARCH, 87, 2718-2727.

Desacyl-ghrelin and Synthetic GH-secretagogues Modulate the Production of Inflammatory Cytokines in Mouse Microglia Cells Stimulated by beta-Amyloid Fibrils

BULGARELLI, ILARIA;TAMIAZZO, LAURA;BRESCIANI, ELENA;CAPORALI, SIMONA;LOCATELLI, VITTORIO;TORSELLO, ANTONIO BIAGIO
2009

Abstract

Data from Alzheimer's disease (AD) patients and AD animal models demonstrate the accumulation of inflammatory microglia at sites of insoluble fibrillar β-amyloid protein (fAβ) deposition. It is known that fAβ binds to CD36, a type B scavenger receptor also involved in internalization of oxidized low-density lipoprotein (LDL), and initiate a signaling cascade that regulates microglial recruitment, activation, and secretion of inflammatory mediators leading to neuronal dysfunction and death. The recent demonstration of a binding site for the growth hormone secretagogues (GHS) on CD36 prompted us to ascertain whether ghrelin and synthetic GHS could modulate the synthesis of inflammatory cytokines in fAβ-activated microglia cells. We demonstrate that N9 microglia cells express the CD36 and are a suitable model to study the activation of inflammatory cytokines synthesis. In fact, in N9 cells exposed to fAβ25-35 for 24 hr, the expression of interleukin (IL)-1β and IL-6 mRNA significantly increased. Interestingly, 10-7 M desacyl-ghrelin, hexarelin, and EP80317 in the nanomolar range effectively counteracted fAβ25-35 stimulation of IL-6 mRNA levels, whereas ghrelin was ineffective. Similarly, the effects of fAβ25-35 on IL-1b mRNA levels were attenuated by desacyl-ghrelin, hexarelin, and EP80317, but not ghrelin. Because we have observed that the specific GHS receptor GHS-R1a is not expressed in N9 cells, the actions of GHS should be mediated by different receptors. Reportedly, hexarelin and EP80317 are capable of binding the CD36 in mouse macrophages and reducing atherosclerotic plaque deposition in mice. We conclude that desacyl-ghrelin, hexarelin, and EP80317 might interfere with fAβ activation of CD36 in microglia cells. © 2009 Wiley-Liss, Inc.
Articolo in rivista - Articolo scientifico
ghrelin, microglia, cytokines, amyloid
English
2009
87
2718
2727
none
Bulgarelli, I., Tamiazzo, L., Bresciani, E., Rapetti, D., Caporali, S., Lattuada, D., et al. (2009). Desacyl-ghrelin and Synthetic GH-secretagogues Modulate the Production of Inflammatory Cytokines in Mouse Microglia Cells Stimulated by beta-Amyloid Fibrils. JOURNAL OF NEUROSCIENCE RESEARCH, 87, 2718-2727.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10281/13045
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