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

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-? (TNF-?) and interleukin-1? (IL-1?) induce damage in brain endothelial cells and BBB dysfunction which contribute to neuronal injury. The neuroprotective effects of ?-melanocyte stimulating hormone (?-MSH) were investigated in experimental models, but there are no data related to the BBB. Based on our recent study, in which ?-MSH reduced barrier dysfunction in human intestinal epithelial cells induced by TNF-? and IL-1?, we hypothesized a protective effect of ?-MSH on brain endothelial cells. We examined the effect of these two pro-inflammatory cytokines, and the neuropeptide ?-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-? and IL-1? induced cell damage, measured by impedance and MTT assay, which was attenuated by ?-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 ?-catenin. Elevated production of reactive oxygen species and the nuclear translocation of NF-?B were also reduced by ?-MSH in brain endothelial cells stimulated by cytokines. We demonstrated for the first time the direct beneficial effect of ?-MSH on cultured brain endothelial cells, indicating that this neurohormone may be protective at the BBB.

SUBMITTER: Harazin A 

PROVIDER: S-EPMC5958884 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature