Capmatinib suppresses LPS-induced interaction between HUVECs and THP-1 monocytes through suppression of inflammatory responses.

Abstract

BACKGROUND:

Capmatinib (CAP) is a drug that has been used to treat non-small cell lung cancer (NSCLC) in adults. Presently, its novel effects on skeletal muscle insulin signaling, inflammation, and lipogenesis in adipocytes have been uncovered with a perspective of drug repositioning. However, the impact of CAP on LPS-mediated interaction between human umbilical vein endothelial cells (HUVECs) and THP-1 monocytes has yet to be investigated.

METHODS:

HUVECs and THP-1 monocytes were treated with LPS and CAP. The protein expression levels were determined using Western blotting. Target protein knockdown was conducted using small interfering (si) RNA transfection. Interactions between HUVECs and THP-1 cells were assayed using green fluorescent dye.

RESULTS:

This study found that CAP treatment ameliorated cell adhesion between THP-1 monocytes and HUVECs and the expression of adhesive molecules, such as intracellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and E-selectin. Moreover, phosphorylation of inflammatory markers, such as NFκB and IκB as well as TNFα and monocyte chemoattractant protein-1 (MCP-1) released from HUVECs and THP-1 monocytes, was prevented by CAP treatment. Treatment with CAP augmented PPARδ and IL-10 expression. siRNA-associated suppression of PPARδ and IL-10 abolished the effects of CAP on cell interaction between HUVECs and THP-1 cells and inflammatory responses. Further, PPARδ siRNA mitigated CAP-mediated induction of IL-10 expression.

CONCLUSION:

These findings imply that CAP improves inflamed endothelial-monocyte adhesion via a PPARδ/IL-10-dependent pathway. The current study provides in vitro evidence for a therapeutic approach for treating atherosclerosis.

• Authors: Hyung Sub Park, A M Abd El-Aty, Ji Hoon Jeong, Taeseung Lee, Tae Woo Jung
• Journal: Biomedical journal (Biomed J) Vol. 46 Issue 2 Pg. 100534 (04 2023) ISSN: 2320-2890 [Electronic] United States
• PMID: 35483573 (Publication Type: Journal Article)
• Copyright: Copyright © 2022 Chang Gung University. Published by Elsevier B.V. All rights reserved.

Chemical References

• Interleukin-10
• Lipopolysaccharides
• capmatinib
• PPAR delta
• RNA, Small Interfering
• Intercellular Adhesion Molecule-1

Topics

• Humans
• Monocytes (metabolism)
• Human Umbilical Vein Endothelial Cells (metabolism)
• Interleukin-10
• Lipopolysaccharides (pharmacology, metabolism)
• PPAR delta (metabolism, pharmacology)
• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• RNA, Small Interfering (metabolism, pharmacology)
• Intercellular Adhesion Molecule-1 (metabolism, pharmacology)