Protection of cultured brain endothelial cells from cytokine-induced damage by α-melanocyte stimulating hormone

András Harazin, Alexandra Bocsik, Lilla Barna, András Kincses, J. Váradi, Ferenc Fenyvesi, Vilmos Tubak, Maria A. Deli, M. Vecsernyés

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

The blood-brain barrier (BBB), an interface between the systemic circulation and the nervous system, can be a target of cytokines in inflammatory conditions. Pro-inflammatory cytokines tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) induce damage in brain endothelial cells and BBB dysfunction which contribute to neuronal injury. The neuroprotective effects of α-melanocyte stimulating hormone (α-MSH) were investigated in experimental models, but there are no data related to the BBB. Based on our recent study, in which α-MSH reduced barrier dysfunction in human intestinal epithelial cells induced by TNF-α and IL-1β, we hypothesized a protective effect of α-MSH on brain endothelial cells. We examined the effect of these two pro-inflammatory cytokines, and the neuropeptide α-MSH on a culture model of the BBB, primary rat brain endothelial cells cocultured with rat brain pericytes and glial cells. We demonstrated the expression of melanocortin-1 receptor in isolated rat brain microvessels and cultured brain endothelial cells by RT-PCR and immunohistochemistry. TNF-α and IL-1β induced cell damage, measured by impedance and MTT assay, which was attenuated by α-MSH (1 and 10 pM). The peptide inhibited the cytokine-induced increase in brain endothelial permeability, and restored the morphological changes in cellular junctions visualized by immunostaining for claudin-5 and β-catenin. Elevated production of reactive oxygen species and the nuclear translocation of NF-kB were also reduced by α-MSH in brain endothelial cells stimulated by cytokines. We demonstrated for the first time the direct beneficial effect of α-MSH on cultured brain endothelial cells, indicating that this neurohormone may be protective at the BBB.

Original languageEnglish
Article numbere4774
JournalPeerJ
Volume2018
Issue numberMAY
DOIs
Publication statusPublished - Jan 1 2018

Fingerprint

melanocyte-stimulating hormone
Melanocyte-Stimulating Hormones
Endothelial cells
endothelial cells
Brain
cytokines
Endothelial Cells
blood-brain barrier
Cytokines
brain
Blood-Brain Barrier
tumor necrosis factors
interleukin-1
Interleukin-1
Rats
Tumor Necrosis Factor-alpha
rats
Claudin-5
Receptor, Melanocortin, Type 1
neurohormones

Keywords

  • Blood-brain barrier
  • Brain endothelial cells
  • Cytokines
  • Melanocortin-1 receptor
  • Permeability
  • Reactive oxygen species
  • Tight junction
  • α-Melanocyte-stimulating hormone

ASJC Scopus subject areas

  • Neuroscience(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Protection of cultured brain endothelial cells from cytokine-induced damage by α-melanocyte stimulating hormone. / Harazin, András; Bocsik, Alexandra; Barna, Lilla; Kincses, András; Váradi, J.; Fenyvesi, Ferenc; Tubak, Vilmos; Deli, Maria A.; Vecsernyés, M.

In: PeerJ, Vol. 2018, No. MAY, e4774, 01.01.2018.

Research output: Contribution to journalArticle

Harazin, András ; Bocsik, Alexandra ; Barna, Lilla ; Kincses, András ; Váradi, J. ; Fenyvesi, Ferenc ; Tubak, Vilmos ; Deli, Maria A. ; Vecsernyés, M. / Protection of cultured brain endothelial cells from cytokine-induced damage by α-melanocyte stimulating hormone. In: PeerJ. 2018 ; Vol. 2018, No. MAY.
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