The mechanisms that regulate inflammatory cell recruitment across the blood-brain barrier (BBB) during CNS inflammation have not been fully characterized. Likely players in this process include the chemokines, small secondary messengers of inflammation capable of subset-specific leukocyte activation and chemoattraction. Primary cultures of human brain microvessel endothelial cells (HBMEC) were examined for their in vitro expression of the beta chemokines RANTES and MIP-1␤. Untreated HBMEC

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... sed low levels of RANTES and MIP-1␤ RNA that were significantly upregulated following cytokine treatment. Parallel studies performed on human umbilical vein endothelial cells (HUVEC) showed induction of RANTES but not MIP-1␤ RNA. Following stimulation with LPS, TNF-␣, IFN-␥, and IL-1␤ alone or in combination, HBMEC released significant amounts of RANTES and MIP-1␤ into the culture supernatants. RANTES secretion by HUVEC could be induced only with TNF-␣/IFN-␥. Both RANTES and MIP-1␤ were detected by immunocytochemistry on the apical and basal surfaces of HBMEC, as well as bound to basal lamina-like material under the basal cell surface. Cytokine stimulation induced significant increase of RANTES and MIP-1␤ molecules associated with the EC surface and subendothelial matrix. The expression of RANTES and MIP-1␤ by HBMEC suggests that these chemokines may play an important role in mediating inflammatory responses and leukocyte trafficking across the BBB.