A Polymeric Nanomedicine Diminishes Inflammatory Events in Renal Tubular Cells

作者：Ucero Alvaro C; Berzal Sergio; Ocana Salceda Carlos; Sancho Monica; Orzaez Mar; Messeguer Angel; Ruiz Ortega Marta; Egido Jesus; Vicent Maria J; Ortiz Alberto; Ramos Adrian M^*

来源：PLos One, 2013, 8(1): e51992.

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. %26lt;br%26gt;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-kappa B activation. Similar to JAK2 kinase inhibitors, QM56 inhibited Tweak-induced NF-kappa B transcriptional activity and chemokine expression, despite failing to inhibit NF-kappa B-p65 nuclear translocation and NF-kappa B DNA binding. QM56 prevented JAK2 activation and NF-kappa B-p65(Ser536) phosphorylation. The anti-inflammatory effect and JAK2 inhibition by QM56 were observed in Apaf-1(-/-) cells. %26lt;br%26gt;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.

• 出版日期2013-1-2