MECHANISMS OF HYALURONAN-INDUCED UP-REGULATION OF ICAM-1 AND VCAM-1 EXPRESSION BY MURINE KIDNEY TUBULAR EPITHELIAL-CELLS - HYALURONAN TRIGGERS CELL-ADHESION MOLECULE EXPRESSION THROUGH A MECHANISM INVOLVING ACTIVATION OF NUCLEAR FACTOR-KAPPA-B AND ACTIVATING PROTEIN-1
B. Oertli et al., MECHANISMS OF HYALURONAN-INDUCED UP-REGULATION OF ICAM-1 AND VCAM-1 EXPRESSION BY MURINE KIDNEY TUBULAR EPITHELIAL-CELLS - HYALURONAN TRIGGERS CELL-ADHESION MOLECULE EXPRESSION THROUGH A MECHANISM INVOLVING ACTIVATION OF NUCLEAR FACTOR-KAPPA-B AND ACTIVATING PROTEIN-1, The Journal of immunology (1950), 161(7), 1998, pp. 3431-3437
The matrix constituent hyaluronan (HA) markedly accumulates in inflamm
atory lesions. To gain insight into the biologic significance of this
phenomenon we tested the hypothesis that HA could regulate cell adhesi
on molecule expression in epithelial cells. Using a clonal line of mou
se cortical tubular (MCT) cells we found that fragmented intermediate
m.w., but not high m.w., HA markedly increased ICAM-1 and VCAM-1 stead
y state mRNA and cell surface expression. Up-regulation of ICAM-1 and
VCAM-1 mRNA by HA was preceded by a marked increase in NF-kappa B and
activating protein-1 DNA binding activity in MCT cells. Transcript lev
els for the NF-kappa B inhibitor I kappa B alpha and for the activatin
g protein-1 constituents c-jun and c-fos also increased in response to
HA stimulation of-tubular cells. Inhibition of NF-kappa B with the se
rine protease inhibitor N-tosyl-L-phenylalanine chloromethyl ketone bl
ocked the HA-mediated expression of ICAM-1 and VCAM-1 in MCT cells, In
conclusion, ZIA displays proinflammatory effects by directly stimulat
ing the expression; of the cell adhesion molecules ICAM-1 and VCAM-1 i
n mouse kidney epithelial cells. HA could thereby play an important ro
le in leukocyte adhesion in inflammatory renal diseases.