Title |
A Polymeric Nanomedicine Diminishes Inflammatory Events in Renal Tubular Cells
|
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Published in |
PLOS ONE, January 2013
|
DOI | 10.1371/journal.pone.0051992 |
Pubmed ID | |
Authors |
Álvaro 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. |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Unknown | 28 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Researcher | 6 | 21% |
Student > Ph. D. Student | 4 | 14% |
Student > Bachelor | 3 | 11% |
Student > Doctoral Student | 2 | 7% |
Professor | 2 | 7% |
Other | 5 | 18% |
Unknown | 6 | 21% |
Readers by discipline | Count | As % |
---|---|---|
Agricultural and Biological Sciences | 6 | 21% |
Biochemistry, Genetics and Molecular Biology | 5 | 18% |
Medicine and Dentistry | 5 | 18% |
Nursing and Health Professions | 2 | 7% |
Chemistry | 2 | 7% |
Other | 2 | 7% |
Unknown | 6 | 21% |