Difference in cytokines, chemokines and growth factors produced by blood–brain barrier‐ and blood–nerve barrier‐composing cells

Abstract

AbstractObjectivesThe blood–brain barrier (BBB) and blood–nerve barrier (BNB) comprise the brain/peripheral nerve‐specific barrier system, formed by microvascular endothelial cells, pericytes and astrocytes in the BBB, and microvascular endothelial cells and pericytes in the BNB. The differences in the detailed cellular biology among these cells are still unclear. The purpose of the present study was to quantify and compare the cytokine/chemokine/growth factor levels in BBB‐ and BNB‐ composing cells.MethodsWe quantified the levels of 27 cytokines/chemokines/growth factors in human umbilical vein endothelial cells, human brain and peripheral nerve microvascular endothelial cells, pericytes, and astrocytes using a multiplexed fluorescent bead‐based immunoassay system.ResultsBasic fibroblast growth factor and regulated on activation, normal T cell expressed and secreted were mainly produced by both astrocytes and peripheral pericytes. Vascular endothelial growth factor and interferon‐inducible protein of 10 kDa were secreted by astrocytes. Interleukin‐1β, interleukin‐6, interleukin‐8 and macrophage chemoattractant protein‐1 were produced more abundantly by brain and peripheral nerve pericytes than by astrocytes. Larger amounts of basic fibroblast growth factor; interferon‐inducible protein of 10 kDa; regulated on activation, normal T cell expressed and secreted; and tumor necrosis factor‐α were secreted by brain microvascular endothelial cells than by peripheral nerve microvascular endothelial cells or human umbilical vein endothelial cells.ConclusionsSimilar to brain pericytes and astrocytes, peripheral nerve pericytes produce several cytokines, chemokines and growth factors. This suggests that these cells contribute to the barrier functions in the BNB, in the same manners as brain pericytes and astrocytes do in the BBB.