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

Citation
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
Citations number
45
Categorie Soggetti
Immunology
ISSN journal
00221767
Volume
161
Issue
7
Year of publication
1998
Pages
3431 - 3437
Database
ISI
SICI code
0022-1767(1998)161:7<3431:MOHUOI>2.0.ZU;2-T
Abstract
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.