A polymeric nanomedicine diminishes inflammatory events in renal tubular cells

• Published in: PloS one 2013-01, Vol.8 (1), p.e51992
• Main Authors: Ucero, Alvaro C, Berzal, Sergio, Ocaña-Salceda, Carlos, Sancho, Mónica, Orzáez, Mar, Messeguer, Angel, Ruiz-Ortega, Marta, Egido, Jesús, Vicent, María J, Ortiz, Alberto, Ramos, Adrián M
• Format: Article
• Language: English
• Subjects: Active Transport, Cell Nucleus; Animal models; Animals; Anti-inflammatory agents; Anti-Inflammatory Agents - pharmacology; Apaf-1 protein; Apoptosis; Binding; Biology; Cell activation; Cell culture; Cell Line; Chemistry; Chemokine CCL2 - metabolism; Chemokine CCL5 - metabolism; Chemokines; Cytochrome; Cytokines; Deoxyribonucleic acid; Disease Models, Animal; DNA; Gene expression; Health aspects; Infiltration; Inflammation; Inflammation - pathology; Inflammatory response; Janus kinase 2; Janus Kinase 2 - metabolism; Kidney - metabolism; Kidney - pathology; Kidney diseases; Kidney Tubules - pathology; Laboratory animals; Medicine; Mice; Mice, Inbred C57BL; Monocyte chemoattractant protein 1; Nanoconjugates; Nanomedicine; Nanomedicine - methods; Nanoparticles - chemistry; Nanotechnology; Nephrology; NF-kappa B - metabolism; NF-κB protein; Nuclear transport; Pathology; Peptoids - chemistry; Peptoids - pharmacology; Pharmaceutical sciences; Phosphorylation; Polyglutamic Acid - analogs & derivatives; Polyglutamic Acid - chemistry; Polyglutamic Acid - pharmacology; Proteins; RANTES; Transcription; Translocation; Tumor necrosis factor-TNF
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0051992

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.