Borrelia burgdorferi activates nuclear factor-kappa B and is a potent inducer of chemokine and adhesion molecule gene expression in endothelial cells and fibroblasts.
Lyme disease, caused by the tick-borne spirochete Borrelia burgdorferi, is a systemic infection with preponderance for the skin, joints, heart, and nervous system. Inflammatory lesions of target organs are characterized by the presence of spirochetes and inflammatory leukocytes. We have analyzed the potential of B. burgdorferi to induce gene expression of chemokines and adhesion molecules in human endothelial cells, keratinocytes, and fibroblasts. We find induction of the chemokines RANTES (regulated upon activation, normal T cells expressed and secreted), monocyte chemoattractant protein-1, IL-8, gro-alpha, IFN-inducible protein-10, and mig (monokine induced by gamma-IFN), and of the adhesion molecules E-selectin, ICAM-1, and VCAM-1 in endothelial cells and induction of the same chemokines and ICAM-1 in fibroblasts. This is mediated by the lipid moiety of the outer surface lipoprotein A. Induction of chemokine and adhesion molecule genes by B. burgdorferi occurs rapidly and does not require new protein synthesis. Induction is blocked by inhibitors of nuclear factor (NF)-kappa B. We also find that B. burgdorferi induces nuclear translocation of NF-kappa B and a transient increase in the expression of its inhibitor I kappa B-alpha. These findings indicate that B. burgdorferi is a potent inducer of molecules required for leukocyte recruitment to inflammatory foci, and the data suggest that this biologic activity is due to the ability of the spirochetes to activate the pleiotropic transcription factor NF-kappa B.
Ebnet
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Experimental Immunology Branch, National Cancer Institute, Bethesda, MD 20892, USA. ebnetk@uni-muenster.de
Brown
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Siebenlist
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UK
Simon
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MM
Shaw
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D000954:Antigens, Surface / Q000737:chemistry / Q000494:pharmacology; D001425:Bacterial Outer Membrane Proteins / Q000737:chemistry / Q000494:pharmacology; D001428:Bacterial Vaccines; D001692:Biological Transport / Q000187:drug effects / Q000235:genetics; D015748:Borrelia burgdorferi Group / Q000276:immunology*; D015815:Cell Adhesion Molecules / Q000096:biosynthesis / Q000187:drug effects / Q000235:genetics*; D002460:Cell Line; D002467:Cell Nucleus / Q000235:genetics; D018925:Chemokines / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics; D004730:Endothelium, Vascular / Q000378:metabolism*; D005347:Fibroblasts / Q000378:metabolism; D015964:Gene Expression Regulation, Bacterial / Q000276:immunology*; D006801:Humans; D020672:I-kappa B Proteins; D008074:Lipoproteins / Q000494:pharmacology; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis; D012867:Skin / Q000166:cytology
D000954:Antigens, Surface; D001425:Bacterial Outer Membrane Proteins; D001428:Bacterial Vaccines; D015815:Cell Adhesion Molecules; D018925:Chemokines; D004268:DNA-Binding Proteins; C083487:I kappa B beta protein; D020672:I-kappa B Proteins; D008074:Lipoproteins; D016328:NF-kappa B; C072045:OspA protein; D012333:RNA, Messenger