NDLI: A polymeric nanomedicine diminishes inflammatory events in renal tubular cells.

Content Provider	Directory of Open Access Journals (DOAJ)
Author	Alvaro C. Ucero Sergio Berzal Carlos Ocaña-Salceda Mónica Sancho Mar Orzáez Angel Messeguer Marta Ruiz-Ortega Jesús Egido María J. Vicent Alberto Ortiz Adrián M. Ramos
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.
e-ISSN	19326203
DOI	10.1371/journal.pone.0051992
Journal	PLoS ONE
Issue Number	1
Volume Number	8
Language	English
Publisher	Public Library of Science (PLoS)
Publisher Date	2013-01-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Medicine Science
Content Type	Text
Resource Type	Article

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