title: A polymeric nanomedicine diminishes inflammatory events in renal tubular cells.
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.
authors.affiliation: Laboratory of Nephrology and Vascular Pathology, Instituto de Investigación Sanitaria-Fundación Jiménez Díaz, Madrid, Spain.
authors.forename: Alvaro C
authors.initials: AC
authors.lastname: Ucero
authors.forename: Sergio
authors.initials: S
authors.lastname: Berzal
authors.forename: Carlos
authors.initials: C
authors.lastname: Ocaña-Salceda
authors.forename: Mónica
authors.initials: M
authors.lastname: Sancho
authors.forename: Mar
authors.initials: M
authors.lastname: Orzáez
authors.forename: Angel
authors.initials: A
authors.lastname: Messeguer
authors.forename: Marta
authors.initials: M
authors.lastname: Ruiz-Ortega
authors.forename: Jesús
authors.initials: J
authors.lastname: Egido
authors.forename: María J
authors.initials: MJ
authors.lastname: Vicent
authors.forename: Alberto
authors.initials: A
authors.lastname: Ortiz
authors.forename: Adrián M
authors.initials: AM
authors.lastname: Ramos
mesh_terms: D021581:Active Transport, Cell Nucleus; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D017209:Apoptosis; D002460:Cell Line; D018932:Chemokine CCL2 / Q000378:metabolism; D018946:Chemokine CCL5 / Q000378:metabolism; D004195:Disease Models, Animal; D007249:Inflammation / Q000473:pathology*; D053614:Janus Kinase 2 / Q000378:metabolism; D007668:Kidney / Q000378:metabolism / Q000473:pathology; D007684:Kidney Tubules / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000378:metabolism; D058726:Nanoconjugates; D050997:Nanomedicine / Q000379:methods*; D053758:Nanoparticles / Q000737:chemistry; D034444:Peptoids / Q000737:chemistry / Q000494:pharmacology*; D011099:Polyglutamic Acid / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000893:Anti-Inflammatory Agents; C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D018946:Chemokine CCL5; D016328:NF-kappa B; D058726:Nanoconjugates; D034444:Peptoids; D011099:Polyglutamic Acid; C507926:Jak2 protein, mouse; D053614:Janus Kinase 2