Gene interactions and pathways from curated databases and text-mining
Eur J Clin Invest 1999, PMID: 10583443

Anti-PR-3 antibodies induce endothelial IL-8 release.

Mayet, W; Schwarting, A; Barreiros, A P; Schlaak, J; Neurath, M

BACKGROUND

It has been shown that interaction of anti-PR-3 antibodies with human endothelial cells (EC) leads to an activation of EC in vitro, i.e. induction of adhesion molecules like E-selectin, VCAM-1 and tissue factor. The aim of this study was to investigate the effect of anti-PR-3 antibodies on endothelial IL-8 expression.

METHODS

EC were cultured in 96-well plates and stimulated with TNF-alpha and IL-1beta for 1 h to induce membrane expression of endothelial PR-3. Anti-PR-3 antibodies were purified from sera from patients with clinically active Wegener's granulomatosis. Purified anti-Ro, anti-centromere, anti-dsDNA antibodies and a monoclonal anti-PR-3 antibody (WGM2) served as controls. Induction of IL-8 mRNA was detected by RT-PCR. IL-8 was measured in the supernatant of EC by ELISA. In addition, induction of NFkappaB was investigated by PAGE of nuclear extracts of EC and Western blot with ab against p65.

RESULTS

In contrast to controls, interaction of anti-PR-3 antibodies (patients and WGM2) with cytokine activated EC led to the highest amount of IL-8 synthesis. Priming of EC with cytokines alone induced a markedly lower IL-8 level. The lowest levels of IL-8 could be measured after incubation of unprimed EC with anti-PR-3 antibodies. Anti-PR-3 antibody induced endothelial IL-8 expression could be inhibited by cycloheximide. In addition, we established that the activation of NF-kappaB is critically involved in anti-PR-3 antibody induced endothelial IL-8 production.

CONCLUSIONS

In summary, we were able to show that anti-PR-3 antibodies induce endothelial IL-8 synthesis by activating NF-kappaB. As IL-8 represents a powerful neutrophil chemoattractant, our data provide further evidence for a direct pathogenic effect of anti-PR-3 antibodies in ANCA related diseases.

Diseases/Pathways annotated by Medline MESH: Wegener Granulomatosis
Document information provided by NCBI PubMed

Text Mining Data

IL-8 — NF-kappaB: " In addition, we established that the activation of NF-kappaB is critically involved in anti-PR-3 antibody induced endothelial IL-8 production "

Manually curated Databases

No curated data.