+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

Ghrelin Attenuates Neuroinflammation and Demyelination in Experimental Autoimmune Encephalomyelitis Involving NLRP3 Inflammasome Signaling Pathway and Pyroptosis



Ghrelin Attenuates Neuroinflammation and Demyelination in Experimental Autoimmune Encephalomyelitis Involving NLRP3 Inflammasome Signaling Pathway and Pyroptosis



Frontiers in Pharmacology 10: 1320



Multiple sclerosis (MS) is a chronic autoimmune and degenerative disease of the central nervous system, and conventional treatments have limited efficacy or side effects. Ghrelin, a 28-amino acid octanoylated peptide, has been reported to have neuroprotective effects, including anti-oxidation, anti-inflammation, and anti-apoptosis. Pyroptosis, also called inflammatory cell death, is triggered by overly active inflammasomes and accompanied by the production of numerous cytokines. As immune dysfunction is primarily involved in the pathogenesis of MS, this study aimed to explore the therapeutic effects and precise functional mechanisms of ghrelin against the nod-like receptor protein 3 (NLRP3) inflammasome and pyroptosis in experimental autoimmune encephalomyelitis (EAE). Sprague Dawley rats were immunized with guinea pig spinal cord homogenates and pertussis toxin to develop an EAE model. All rats were randomly divided into four groups: normal control group, EAE group, EAE + ghrelin group, and ghrelin control group. EAE rats showed abnormal behavioral scores and body weight changes. Histologic analysis displayed severe inflammatory infiltration and demyelination in the brain and spinal cord of EAE rats. Ghrelin treatments potently restored these abnormal changes. In addition, the ghrelin-treated EAE group showed significantly downregulated expression of inflammatory cytokines. The expression of proteins involved in the NLRP3 signaling pathway and pyroptosis was decreased as well. We also found that the anti-inflammatory effect of ghrelin was associated with inhibition of nuclear factor (NF)-κB activation. Compared with rats in the healthy control group, rats in the ghrelin control group did not show statistically significant changes in histologic examinations, pro-inflammatory cytokines production, or molecules involved in the NLRP3 signaling pathway, which indicated that ghrelin induced no side effects in the animals of our study. Our findings provide more insight into the use of ghrelin as a novel candidate for MS.

Please choose payment method:






(PDF emailed within 1 workday: $29.90)

Accession: 069565034

Download citation: RISBibTeXText

PMID: 31780940


Related references

Liraglutide attenuates NLRP3 inflammasome-dependent pyroptosis via regulating SIRT1/NOX4/ROS pathway in H9c2 cells. Biochemical and Biophysical Research Communications 499(2): 267-272, 2018

Cholecalciterol cholesterol emulsion attenuates experimental autoimmune myocarditis in mice via inhibition of the pyroptosis signaling pathway. Biochemical and Biophysical Research Communications 493(1): 422-428, 2017

Dihydromyricetin inhibits NLRP3 inflammasome-dependent pyroptosis by activating the Nrf2 signaling pathway in vascular endothelial cells. Biofactors 44(2): 123-136, 2018

Regulation of the NLRP3 inflammasome and macrophage pyroptosis by the p38 MAPK signaling pathway in a mouse model of acute lung injury. Molecular Medicine Reports 18(5): 4399-4409, 2018

NLRP3 inflammasome induces chemotactic immune cell migration to the CNS in experimental autoimmune encephalomyelitis. Proceedings of the National Academy of Sciences of the United States of America 109(26): 10480-5, 2012

Activating cannabinoid receptor 2 alleviates pathogenesis of experimental autoimmune encephalomyelitis via activation of autophagy and inhibiting NLRP3 inflammasome. Cns Neuroscience and Therapeutics 20(12): 1021-1028, 2014

MicroRNA‑223 attenuates LPS‑induced inflammation in an acute lung injury model via the NLRP3 inflammasome and TLR4/NF‑κB signaling pathway via RHOB. International Journal of Molecular Medicine 43(3): 1467-1477, 2019

Y-39983, a selective Rho-kinase inhibitor, attenuates experimental autoimmune encephalomyelitis via inhibition of demyelination. Neuroimmunomodulation 20(6): 334-340, 2013

3-(Naphthalen-2-yl(propoxy)methyl)azetidine hydrochloride attenuates NLRP3 inflammasome-mediated signaling pathway in lipopolysaccharide-stimulated BV2 microglial cells. Biochemical and Biophysical Research Communications 495(1): 151-156, 2018

Ghrelin attenuates UUO-induced renal fibrosis via attenuation of Nlrp3 inflammasome and endoplasmic reticulum stress. American Journal of Translational Research 11(1): 131-141, 2019

Gut Microbial Products and Saturated Fatty Acids Lead to Nitrergic Enteric Neuronal Pyroptosis via Activation of Ros-Mediated Nek7/Nlrp3 Inflammasome Pathway. Gastroenterology 154(6): S-55-S-56, 2018

Endogenous hydrogen sulphide attenuates NLRP3 inflammasome-mediated neuroinflammation by suppressing the P2X7 receptor after intracerebral haemorrhage in rats. Journal of Neuroinflammation 14(1): 163, 2017

Direct angiotensin type 2 receptor (AT2R) stimulation attenuates T-cell and microglia activation and prevents demyelination in experimental autoimmune encephalomyelitis in mice. Clinical Science 128(2): 95, 2015

Limiting Neuronal Nogo Receptor 1 Signaling during Experimental Autoimmune Encephalomyelitis Preserves Axonal Transport and Abrogates Inflammatory Demyelination. Journal of Neuroscience 39(28): 5562-5580, 2019

Ghrelin protects the heart against ischemia/reperfusion injury via inhibition of TLR4/NLRP3 inflammasome pathway. Life Sciences 186: 50-58, 2017