2026-06-14T03:31:27Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/110972024-09-27T08:07:46Zcom_20.500.12105_19604com_20.500.12105_2051col_20.500.12105_19605
Repisalud
author
Roche-Molina, Marta
author
Hardwick, Bryn
author
Sanchez-Ramos, Cristina
author
Sanz-Rosa, David
author
Gewert, Dirk
author
Cruz, Francisco Miguel
author
Gonzalez-Guerra, Andres
author
Andres, Vicente
author
Palma, Joaquin A
author
Ibáñez, Borja
author
Mckenzie, Grahame
author
Bernal, Juan Antonio
funder
Ministerio de Ciencia, Innovación y Universidades (España)
funder
Fundación ProCNIC
2020-10-06T13:39:28Z
2020-10-06T13:39:28Z
2020-07-15
Sci Rep. 2020; 10(1):11636
10.1038/s41598-020-68350-2
2045-2322
Scientific reports
32669659
http://hdl.handle.net/20.500.12105/11097
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 that inclusion of bioactive solvent NMP in pharmaceutical compositions to treat inflammatory disorders might be beneficial and safe, in particular to treat diseases of the vascular system, such as atherosclerosis.
eng
The pharmaceutical solvent N-methyl-2-pyrollidone (NMP) attenuates inflammation through Krüppel-like factor 2 activation to reduce atherogenesis.
journal article
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