BORRELIA-BURGDORFERI OUTER-MEMBRANE PROTEIN-A INDUCES NUCLEAR TRANSLOCATION OF NUCLEAR FACTOR-KAPPA-B AND INFLAMMATORY ACTIVATION IN HUMAN ENDOTHELIAL-CELLS
Rm. Wooten et al., BORRELIA-BURGDORFERI OUTER-MEMBRANE PROTEIN-A INDUCES NUCLEAR TRANSLOCATION OF NUCLEAR FACTOR-KAPPA-B AND INFLAMMATORY ACTIVATION IN HUMAN ENDOTHELIAL-CELLS, The Journal of immunology, 157(10), 1996, pp. 4584-4590
Lyme disease is caused by infection with Borrelia burdorferi, and is c
haracterized by bacterial persistence and inflammation in a number of
host tissues. B. burgdorferi outer surface lipoproteins possess cytoki
ne stimulatory properties that may be responsible for localized inflam
mation. B. burgdorferi presence is correlated with severity of disease
, and the pathology of many tissues, particularly the arthritic joint,
is consistent with localized cytokine production. Spirochete invasion
of tissues requires interaction with and penetration of vascular endo
thelium, suggesting endothelial cells may participate in the inflammat
ion of Lyme disease. In this study, outer surface protein A (OspA), a
model B. burgdorferi lipoprotein, was found to be a potent stimulant o
f nuclear factor-kappa B (NF-kappa B) nuclear translocation in human e
ndothelial cells, resulting in nuclear levels similar to those seen in
response to known inflammatory mediators. Only the lipid-modified Osp
A had activity, and activity was not due to contamination with LPS, Nu
clear NF-kappa B was detectable within 15 min, suggesting that OspA di
rectly mediates NF-kappa B nuclear translocation. OspA also rapidly up
-regulated endothelial cell production of several proteins whose trans
cription is dependent on NF-kappa B: the cytokine IL-6; the chemokine
IL-8; and the adhesion molecules E-selectin, VCAM-1, and ICAM-1. The a
dhesion molecules were functional, as demonstrated by enhanced binding
of neutrophils to OspA-stimulated endothelial monolayers, These data
suggest that OspA may initiate synthesis of many proteins essential fo
r localized inflammation via the direct activation of NF-kappa B-depen
dent transcription. These observations suggest that the interaction of
B. burgdorferi lipoproteins with the endothelium may directly induce
the inflammation responsible for the symptoms of Lyme disease.