Open AccessA Polymeric Nanomedicine Diminishes Inflammatory Events in Renal Tubular Cells
Author(s) -
Álvaro C. Ucero,
Sergio Berzal,
Carlos Ocaña-Salceda,
Mónica Sancho,
Mar Orzáez,
Àngel Messeguer,
Marta Ruíz-Ortega,
Jesús Egido,
Marı́a J. Vicent,
Alberto Ortíz,
Adrián M. Ramos
Publication year - 2013
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0051992
Subject(s) - apoptosis , chemokine , nf κb , inflammation , cancer research , chemistry , kidney , signal transduction , microbiology and biotechnology , iκbα , nfkb1 , pharmacology , biology , immunology , biochemistry , endocrinology , transcription factor , gene
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.