Escherichia coli K1 induces IL-8 expression in human brain microvascular endothelial cells.
Microbial penetration of the blood-brain barrier (BBB) into the central nervous system is essential for the development of meningitis. Considerable progress has been achieved in understanding the pathophysiology of meningitis, however, relatively little is known about the early inflammatory events occurring at the time of bacterial crossing of the BBB. We investigated, using real-time quantitative PCR, the expression of the neutrophil chemoattractants alpha-chemokines CXCL1 (Groalpha) and CXCL8 (IL-8), and of the monocyte chemoattractant beta-chemokine CCL2 (MCP-1) by human brain microvascular endothelial cells (HBMEC) in response to the meningitis-causing E. coli K1 strain RS218 or its isogenic mutants lacking the ability to bind to and invade HBMEC. A nonpathogenic, laboratory E. coli strain HB101 was used as a negative control. CXCL8 was shown to be significantly expressed in HBMEC 4 hours after infection with E. coli K1, while no significant alterations were noted for CXCL1 and CCL2 expression. This upregulation of CXCL8 was induced by E. coli K1 strain RS218 and its derivatives lacking the ability to bind and invade HBMEC, but was not induced by the laboratory strain HB101. In contrast, no upregulation of CXCL8 was observed in human umbilical vein endothelial cells (HUVEC) after stimulation with E. coli RS218. These findings indicate that the CXCL8 expression is the result of the specific response of HBMEC to meningitis-causing E. coli K1.
Galanakis
Emmanouil
E
Division of Pediatric Infectious Diseases, The Johns Hopkins University School of Medicine, Baltimore, 600 N. Wolfe Street, Park 256, Baltimore, Maryland 21287, USA.
Di Cello
Francescopaolo
F
Paul-Satyaseela
Maneesh
M
Kim
Kwang Sik
KS
D001921:Brain / Q000098:blood supply / Q000166:cytology; D002460:Cell Line; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000235:genetics; D054360:Chemokine CXCL1; D019743:Chemokines, CXC / Q000235:genetics; D042783:Endothelial Cells / Q000166:cytology* / Q000378:metabolism / Q000382:microbiology; D004926:Escherichia coli / Q000145:classification / Q000235:genetics / Q000254:growth & development*; D005786:Gene Expression Regulation; D006801:Humans; D016209:Interleukin-8 / Q000235:genetics*; D020814:Meningitis, Escherichia coli / Q000382:microbiology; D009154:Mutation; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013045:Species Specificity; D013997:Time Factors
C475829:CXCL1 protein, human; D018932:Chemokine CCL2; D054360:Chemokine CXCL1; D019743:Chemokines, CXC; D016209:Interleukin-8