Mixed Lineage Kinase Domain-Like Protein Promotes Human Monocyte Cell Adhesion to Human Umbilical Vein Endothelial Cells Via Upregulation of Intercellular Adhesion Molecule-1 Expression.

Abstract

BACKGROUND Atherosclerosis is a progressive inflammatory disease that involves a variety of inflammatory and proinflammatory factors, including intercellular adhesion molecule (ICAM)-1. ICAM-1 plays an important role in atherosclerosis by promoting cell adhesion. Mixed lineage kinase domain-like (MLKL), a critical regulator of necroptotic cell death, is indicated to play an important role in atherosclerosis. This study investigated the effects of MLKL on ICAM-1 expression and cell adhesion, thus providing a new direction for the research of atherosclerosis pathogenesis. MATERIAL AND METHODS siRNA-MLKL and pcDNA-MLKL were designed, and the expression of MLKL and ICAM-1 were estimated by real-time polymerase chain reaction at the mRNA level and Western blotting at the protein level. The adhesion of human monocyte cells (THP-1) to human umbilical vein endothelial cells (HUVECs) was examined under immunofluorescence microscopy, and the ability of cell adhesion was evaluated by ImageJ software. RESULTS Overexpression of MLKL greatly enhanced ICAM-1 expression in HUVECs and the adherence of THP-1 cells to HUVECs. Knockdown of MLKL by siRNA dramatically inhibited the expression of ICAM-1 and the adherence of THP-1 cells to HUVECs. MLKL could promote THP-1 adhesion to HUVECs by activating ICAM-1 expression in HUVECs. CONCLUSIONS MLKL can promote THP-1 cell adhesion to HUVECs through up-regulation of ICAM-1 expression in HUVECs. Thus, MLKL might be a useful target for reducing adhesion of monocytes to endothelial cells and atherosclerosis.

• Authors: Fen Cai, Jia-Li Wang, Yi-Lin Wu, Yan-Wei Hu, Qian Wang
• Journal: Medical science monitor : international medical journal of experimental and clinical research (Med Sci Monit) Vol. 26 Pg. e924242 (Aug 13 2020) ISSN: 1643-3750 [Electronic] United States
• PMID: 32788571 (Publication Type: Journal Article)

Chemical References

• ICAM1 protein, human
• Intercellular Adhesion Molecule-1
• MLKL protein, human
• Protein Kinases

Topics

• Cell Adhesion (physiology)
• Down-Regulation (physiology)
• Endothelium, Vascular (cytology)
• Human Umbilical Vein Endothelial Cells
• Humans
• Intercellular Adhesion Molecule-1 (genetics, physiology)
• Monocytes (cytology)
• Protein Kinases (genetics, physiology)
• Real-Time Polymerase Chain Reaction
• Up-Regulation (physiology)