Endothelial cell adhesiveness is a function of environmental lighting and melatonin level.
The endothelial layer regulates the traffic of cells and substances between the blood and tissues and plays a central role in the mounting of an inflammatory response. We have recently shown that inhibition of the nocturnal melatonin surge during the mounting of an inflammatory response primes endothelial cells to a highly reactive state, increasing the expression of adhesion molecules and inducible nitric oxide synthase (iNOS) as well as the in vitro adherence of leukocytes. Here, we investigated whether physiological variations in the plasma melatonin levels owing to the light/dark environmental cycle could also prime the reactive state of endothelial cells. Cultured endothelial cells (16-20 days) obtained from rats killed during the daytime adhere more neutrophils, expressed more adhesion molecules and iNOS, and had a higher content of the transcription factor nuclear factor kappa B (NF-kB) translocated to the nuclei. We also evaluated the expression of 84 genes (using real-time PCR array) related to the innate inflammatory response and observed a higher expression of 19 genes in cultures obtained during the daytime. In addition, the only gene that was highly expressed in cells obtained from rats killed during nighttime was one that encodes a protein that negatively modulates inflammatory response. In conclusion, the daily rhythm of melatonin also primes the ability of endothelial cells to adhere to neutrophils. This new approach for evaluating the influence of the donor on cells maintained in culture should have applications for the standardization of cell banks.
Laboratory of Chronopharmacology, Department of Physiology, Institute of Biosciences, University of São Paulo, São Paulo, Brazil.
Marina
M
Marçola
Sanseray
S
da Silveira Cruz-Machado
Pedro Augusto Carlos Magno
PA
Fernandes
Alex Willian Arantes
AW
Monteiro
Regina P
RP
Markus
Eduardo Koji
EK
Tamura
D000818:Animals; D024202:Electrophoretic Mobility Shift Assay; D042783:Endothelial Cells / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D008029:Lighting; D008297:Male; D008550:Melatonin / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D009504:Neutrophils / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism*; D051381:Rats
D016328:NF-kappa B; D052247:Nitric Oxide Synthase Type II; D008550:Melatonin