The pharmaceutical solvent N-methyl-2-pyrollidone (NMP) attenuates inflammation through Krüppel-like factor 2 activation to reduce atherogenesis.

Scientific Reports
Marta Roche-MolinaJuan A Bernal

Abstract

N-methyl-2-pyrrolidone (NMP) is a versatile water-miscible polar aprotic solvent. It is used as a drug solubilizer and penetration enhancer in human and animal, yet its bioactivity properties remain elusive. Here, we report that NMP is a bioactive anti-inflammatory compound well tolerated in vivo, that shows efficacy in reducing disease in a mouse model of atherosclerosis. Mechanistically, NMP increases the expression of the transcription factor Kruppel-like factor 2 (KLF2). Monocytes and endothelial cells treated with NMP express increased levels of KLF2, produce less pro-inflammatory cytokines and adhesion molecules. We found that NMP attenuates monocyte adhesion to endothelial cells inflamed with tumor necrosis factor alpha (TNF-α) by reducing expression of adhesion molecules. We further show using KLF2 shRNA that the inhibitory effect of NMP on endothelial inflammation and subsequent monocyte adhesion is KLF2 dependent. Enhancing KLF2 expression and activity improves endothelial function, controls multiple genes critical for inflammation, and prevents atherosclerosis. Our findings demonstrate a consistent effect of NMP upon KLF2 activation and inflammation, biological processes central to atherogenesis. Our data suggest tha...Continue Reading

References

Dec 7, 2002·Behavior Genetics·Alexander A BachmanovMichael G Tordoff
Oct 3, 2003·The New England Journal of Medicine·Jeffrey W MosesUNKNOWN SIRIUS Investigators
May 12, 2004·The Journal of Experimental Medicine·Sucharita SenBanerjeeMukesh K Jain
Oct 7, 2004·Proceedings of the National Academy of Sciences of the United States of America·Guohao DaiMichael A Gimbrone
Mar 1, 2005·Journal of Pharmaceutical Sciences·Philip J LeeV Prasad Shastri
May 10, 2005·The Journal of Biological Chemistry·Kush M ParmarGuillermo García-Cardeña
Dec 13, 2005·The Journal of Clinical Investigation·Kush M ParmarGuillermo García-Cardeña
Apr 18, 2006·Proceedings of the National Academy of Sciences of the United States of America·Hiranmoy DasMukesh K Jain
Jul 21, 2006·Nature·Corey M CarlsonStephen C Jameson
Mar 7, 2007·The Journal of Biological Chemistry·Anne HamikMukesh K Jain
Sep 2, 2008·Circulation Research·G Brandon AtkinsMukesh K Jain
Sep 6, 2008·Nature Nanotechnology·Yenny HernandezJonathan N Coleman
Nov 26, 2008·Nature Clinical Practice. Cardiovascular Medicine·Peter F Davies
Dec 3, 2008·Cell Metabolism·Ralph GareusManolis Pasparakis
Mar 27, 2009·Tissue Engineering. Part a·Blanca San MiguelFranz E Weber
May 6, 2009·Biochemical Pharmacology·Alexander H Sprague, Raouf A Khalil
Aug 12, 2009·Circulation·Giuseppe Danilo NorataAlberico Luigi Catapano
Feb 5, 2011·Science·Jonathan N ColemanValeria Nicolosi
Jan 1, 2010·Journal of Pharmacy & Pharmaceutical Sciences : a Publication of the Canadian Society for Pharmaceutical Sciences, Société Canadienne Des Sciences Pharmaceutiques·Abolghasem JouybanAli Shayanfar
May 20, 2011·Nature·Peter LibbyGöran K Hansson
Nov 3, 2011·Nature Reviews. Cardiology·Michael DomanskiScott Grundy
Dec 6, 2011·Progress in Molecular Biology and Translational Science·José J FusterVicente Andrés
Sep 20, 2012·Proceedings of the National Academy of Sciences of the United States of America·Hong Seok KimReto Asmis
Dec 18, 2012·Arteriosclerosis, Thrombosis, and Vascular Biology·Yao WangJianglin Fan
Mar 6, 2013·Cardiovascular Research·Magnus BäckGiuseppina Caligiuri
Jun 27, 2013·Experimental Cell Research·Kristen T Morin, Robert T Tranquillo
Oct 22, 2013·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·Evan A ThackaberryMinli Xie

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Datasets Mentioned

BETA
AB1700

Methods Mentioned

BETA
PCR
transfection
flow cytometry
RNA-seq
Assay
ELISA

Software Mentioned

IPA
ImageJ
EdgeR
Bioconductor
ZEN
Ingenuity Pathway Analysis
Cell Sens Entry Ink
CASAVA
genebuild
RSEM

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