International Immunology Advance Access originally published online on August 31, 2004
International Immunology 2004 16(10):1467-1475; doi:10.1093/intimm/dxh148
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© 2004 The Japanese Society for Immunology
Interaction of endotoxins with Toll-like receptor 4 correlates with their endotoxic potential and may explain the proinflammatory effect of Brucella spp. LPS
1 Unidad de Investigación, Hospital Clínico Universitario, Valladolid, 2 Departamento de Microbiología, Facultad de Medicina, Universidad de Valladolid and 3 Instituto de Biología y Genética Molecular, CSIC-Universidad de Valladolid, Valladolid, Spain
Correspondence to: M. Sánchez Crespo; E-mail: mscres{at}ibgm.uva.es
Endotoxins displaying differences in the chemical structure of their lipid A were used to induce the expression of chemokines in the human monocytic THP-1 cell line. LPS from two enterobacterial species such as Escherichia coli and Yersinia enterocolitica induced mRNA expression of IFN-
-inducible protein (IP)-10, macrophage-inflammatory protein (MIP)-1
, MIP-1ß, monocyte chemoattractant protein (MCP)-1 and IL-8. LPS from the non-enterobacterial genera Brucella and Ochrobactrum induced the expression of these chemokines to a lower extent. Attempts to address the signaling routes involved in these responses were carried out in transiently transfected HEK293 cells. Induction of 
B-driven transcriptional activity by enterobacterial LPS was observed in cells transfected with TLR-4 alone, although co-transfection of TLR-4, MD-2 and CD14 provided optimal induction. The response to Brucella spp. and Ochrobactrum anthropi LPS was only significant at the concentration of 10 µg/ml. These data indicate that LPS from Brucella spp. and O. anthropi, which contain lipid A moieties with structural features different from those of Enterobacteriaceae elicit biochemical signaling via TLR-4 only at high concentrations. Neither TLR-1, TLR-2 and TLR-6 nor heterodimeric combinations of these receptor molecules are involved. Conversely, the ability of LPS to activate the TLR-4 route is a reliable molecular biomarker for endotoxicity.
Keywords: bacterial infection, chemokines, endotoxin shock, lipopolysaccharide, transcription factors
Transmitting editor: G. Trinchieri
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