2. Academic Validation
  3. IMM-H007, a novel small molecule inhibitor for atherosclerosis, represses endothelium inflammation by regulating the activity of NF-κB and JNK/AP1 signaling

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. 2019 Oct 15;381:114732. doi: 10.1016/j.taap.2019.114732.
Jinjin Yu 1,  Hong Ming 2,  Henry You Li 3,  Bin Yu 4,  Maoping Chu 5,  Haibo Zhu 6,  Xinxing Zhu 7
Affiliations

Affiliations

  • 1 School of psychology, Xinxiang Medical University, Xinxiang 453003, Henan, China. Electronic address: [email protected].
  • 2 Synthetic Biology Engineering Lab of Henan Province, College of Life Sciences and Technology, Xinxiang Medical University, Xinxiang, 453003, Henan, China.
  • 3 Biomolecular Interaction Centre, University of Canterbury, Christchurch 8140, New Zealand.
  • 4 LC-Bio Technologies (Hangzhou) CO., LTD, Hangzhou 310000, Zhejiang, China.
  • 5 Children's Heart Center, the Second Affiliated Hospital and Yuying Children's Hospital, Institute of Cardiovascular Development and Translational Medicine, Wenzhou Medical University, Wenzhou 325000, China.
  • 6 State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Beijing Key Laboratory of New Drug Mechanisms and Pharmacological Evaluation Study, Institute of Materia Medical, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 10050, China. Electronic address: [email protected].
  • 7 Henan Joint International Research Laboratory of Stem Cell Medicine, College of Biomedical Engineering, Xinxiang Medical University, Xinxiang 453003, Henan, China. Electronic address: [email protected].
PMID: 31454633 DOI: 10.1016/j.taap.2019.114732
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.

Keywords

Endothelium Inflammation; H007; JNK/c-Jun Signaling; NF-κB Signaling.

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