BORRELIA-BURGDORFERI ACTIVATES NUCLEAR FACTOR-KAPPA-B AND IS A POTENTINDUCER 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, hea rt, and nervous system. Inflammatory lesions of target organs are char acterized by the presence of spirochetes and inflammatory leukocytes. We have analyzed the potential of B. burgdorferi to induce gene expres sion of chemokines and adhesion molecules in human endothelial cells, keratinocytes, and fibroblasts. We find induction of the chemokines RA NTES (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 adhesi on molecules E-selectin, ICAM-1, and VCAM-1 in endothelial cells and i nduction of the same chemokines and ICAM-1 in fibroblasts. This is med iated by the lipid moiety of the outer surface lipoprotein A. Inductio n of chemokine and adhesion molecule genes by B. burgdorferi occurs ra pidly and does not require new protein synthesis. Induction is blocked by inhibitors of nuclear factor (NF)-kappa B. We also find that B. bu rgdorferi induces nuclear translocation of NF-KB and a transient incre ase in the expression of its inhibitor I kappa B-alpha. These findings indicate that B. burgdorferi is a potent inducer of molecules require d 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-KB.