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.
