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

PeerJ

article

András Harazin¹  Alexandra Bocsik¹  Lilla Barna¹  András Kincses¹  Judit Váradi³  Ferenc Fenyvesi³  Vilmos Tubak⁴  Maria A. Deli¹  Miklós Vecsernyés³ 

[1] Institute of Biophysics, Biological Research Centre, Hungarian Academy of Sciences;Doctoral School in Biology, Faculty of Science and Informatics, University of Szeged;Department of Pharmaceutical Technology, Faculty of Pharmacy, University of Debrecen;Creative Laboratory Ltd.

关键词: Brain endothelial cells;    Permeability;    α-Melanocyte-stimulating hormone;    Cytokines;    Tight junction;    Blood–brain barrier;    Melanocortin-1 receptor;    Reactive oxygen species;   

DOI  :  10.7717/peerj.4774

学科分类：社会科学、人文和艺术（综合）

来源: Inra

【 摘 要 】

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 co-cultured 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-κB 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.

【 授权许可】

CC BY