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B and Activating Protein-11
*
Physiological Institute, University of Zurich-Irchel,
Department of Anesthesiology, and
Division of Nephrology, Department of Medicine, University Hospital, Zurich, Switzerland
The matrix constituent hyaluronan (HA) markedly accumulates in
inflammatory lesions. To gain insight into the biologic significance of
this phenomenon we tested the hypothesis that HA could regulate cell
adhesion molecule expression in epithelial cells. Using a clonal line
of mouse cortical tubular (MCT) cells we found that fragmented
intermediate m.w., but not high m.w., HA markedly increased ICAM-1 and
VCAM-1 steady 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-
B and activating protein-1 DNA binding activity in MCT cells.
Transcript levels for the NF-B inhibitor IB
and for the
activating protein-1 constituents c-jun and
c-fos also increased in response to HA stimulation of
tubular cells. Inhibition of NF-B with the serine protease inhibitor
N-tosyl-L-phenylalanine chloromethyl ketone
blocked the HA-mediated expression of ICAM-1 and VCAM-1 in MCT cells.
In conclusion, HA displays proinflammatory effects by directly
stimulating the expression of the cell adhesion molecules ICAM-1 and
VCAM-1 in mouse kidney epithelial cells. HA could thereby play an
important role in leukocyte adhesion in inflammatory renal
diseases.
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