IMM-H007, a novel small molecule inhibitor for atherosclerosis, represses endothelium inflammation by regulating the activity of NF-κB and JNK/AP1 signaling.
Toxicol Appl Pharmacol
; 381: 114732, 2019 10 15.
Article
em En
| MEDLINE
| ID: mdl-31454633
ABSTRACT
Endothelium inflammation has become a major risk factor for pathological development of atherosclerosis. IMM-H007 (H007), a small molecule compound, is previously reported to reduce inflammatory atherosclerosis. However, the regulatory role of H007 in endothelium inflammation is still unclear. Here, we characterize H007 as a critical repressor in regulation of endothelium inflammation. We find that H007 significantly inhibits monocyte adhesion to endothelial cells and its transendothelial migration. Mechanistically, H007 markedly represses TNFα-induced IκBα degradation and NF-κB nuclear translocation, therefore leading to NF-κB-mediated inflammatory suppression. Moreover, another inflammatory signaling JNK/c-Jun, which is always co-activated with NF-κB in response to pro-inflammatory stimuli, is also found to be restrained by H007 through reducing its phosphorylation status. Thus, we conclude that H007 negatively regulates endothelium inflammation through inactivating NF-κB and JNK/AP1 signaling. More importantly, this study provides us a new insight into understanding the molecular basis by which H007 regulates inflammatory atherosclerosis.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Adenosina
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NF-kappa B
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Fator de Transcrição AP-1
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MAP Quinase Quinase 4
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Anti-Inflamatórios
Tipo de estudo:
Risk_factors_studies
Limite:
Humans
Idioma:
En
Revista:
Toxicol Appl Pharmacol
Ano de publicação:
2019
Tipo de documento:
Article