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PLoS One. 2013;8(1):e51992. doi: 10.1371/journal.pone.0051992. Epub 2013 Jan 2.

A polymeric nanomedicine diminishes inflammatory events in renal tubular cells.

Author information

1
Laboratory of Nephrology and Vascular Pathology, Instituto de Investigación Sanitaria-Fundación Jiménez Díaz, Madrid, Spain.

Abstract

The polyglutamic acid/peptoid 1 (QM56) nanoconjugate inhibits apoptosis by interfering with Apaf-1 binding to procaspase-9. We now describe anti-inflammatory properties of QM56 in mouse kidney and renal cell models.In cultured murine tubular cells, QM56 inhibited the inflammatory response to Tweak, a non-apoptotic stimulus. Tweak induced MCP-1 and Rantes synthesis through JAK2 kinase and NF-κB activation. Similar to JAK2 kinase inhibitors, QM56 inhibited Tweak-induced NF-κB transcriptional activity and chemokine expression, despite failing to inhibit NF-κB-p65 nuclear translocation and NF-κB DNA binding. QM56 prevented JAK2 activation and NF-κB-p65(Ser536) phosphorylation. The anti-inflammatory effect and JAK2 inhibition by QM56 were observed in Apaf-1(-/-) cells. In murine acute kidney injury, QM56 decreased tubular cell apoptosis and kidney inflammation as measured by down-modulations of MCP-1 and Rantes mRNA expression, immune cell infiltration and activation of the JAK2-dependent inflammatory pathway.In conclusion, QM56 has an anti-inflammatory activity which is independent from its role as inhibitor of Apaf-1 and apoptosis and may have potential therapeutic relevance.

PMID:
23300960
PMCID:
PMC3534689
DOI:
10.1371/journal.pone.0051992
[Indexed for MEDLINE]
Free PMC Article

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