Interaction of endotoxins with Toll-like receptor 4 correlates with their endotoxic potential and may explain the proinflammatory effect of Brucella spp. LPS

被引:38
作者
Dueñas, AI
Orduña, A
Crespo, MS [1 ]
García-Rodríguez, C
机构
[1] Univ Valladolid, Inst Biol & Genet Mol, CSIC, Valladolid, Spain
[2] Univ Valladolid, Unidad Invest, Hosp Clin Univ, Valladolid, Spain
[3] Univ Valladolid, Dept Microbiol, Fac Med, Valladolid, Spain
关键词
bacterial infection; chemokines; endotoxin shock; lipopolysaccharide; transcription factors;
D O I
10.1093/intimm/dxh148
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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-gamma-inducible protein (IP)-10, macrophage-inflammatory protein (MIP)-1alpha, MIP-1beta, 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 kappaB-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 mug/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.
引用
收藏
页码:1467 / 1475
页数:9
相关论文
共 52 条
  • [51] Human peripheral blood T cells, monocytes, and macrophages secrete macrophage inflammatory proteins 1α and 1β following stimulation with heat-inactivated Brucella abortus
    Zaitseva, M
    King, LR
    Manischewitz, J
    Dougan, M
    Stevan, L
    Golding, H
    Golding, B
    [J]. INFECTION AND IMMUNITY, 2001, 69 (06) : 3817 - 3826
  • [52] Zhan YF, 1998, J IMMUNOL, V161, P1447