Expression of chemokines and their receptors by human brain endothelium: Implications for multiple sclerosis

Leukocyte migration into the CNS is mediated by chemokines, expressed on the surface of brain endothelium. This study investigated the production of chemokines and expression of chemokine receptors by human brain endothelial cells (HBEC), in vitro and in situ in multiple sclerosis tissue. Four chemokines (CCL2, CCL5, CXCL8 and CXCL10), were demonstrated in endothelial cells in situ, which was reflected in the chemokine production by primary HBEC and a brain endothelial cell line, hCEMC/D3. CXCL8 and CCL2 were constitutively released and increased in response to TNF and/or IFN . CXCL10 and CCL5 were undetectable in resting cells but were secreted in response to these cytokines. TNF strongly increased the production of CCL2, CCL5 and CXCL8, while IFN up-regulated CXCL10 exclusively. CCL3 was not secreted by HBECs and appeared to be confined to astrocytes in situ. The chemokine receptors CXCR1 and CXCR3 were expressed by HBEC both in vitro and in situ, and CXCR3 was up-regulated in response to cytokine stimulation in vitro. By contrast, CXCR3 expression was reduced in silent MS lesions. Brain endothelium expresses particularly high levels of CXCL10 and CXCL8, which may account for the predominant TH1-type inflammatory reaction seen in chronic conditions such as multiple sclerosis