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

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 NFkB and IkB as well as TNFa and monocyte chemoattractant protein-1 (MCP-1) released from HUVECs and THP-1 monocytes, was prevented by CAP treatment. Treatment with CAP augmented PPARd and IL-10 expression. siRNA-associated suppression of PPARd and IL-10 abolished the ef-fects of CAP on cell interaction between HUVECs and THP-1 cells and inflammatory re-sponses. Further, PPARd siRNA mitigated CAP-mediated induction of IL-10 expression.Conclusion: These findings imply that CAP improves inflamed endothelial-monocyte adhesion via a PPARd/IL-10-dependent pathway. The current study provides in vitro evi-dence for a therapeutic approach for treating atherosclerosis.

Journal

BIOMEDICAL JOURNAL

Year

2023

Volume

46

Issue

2

ISSN

2319-4170

eISSN

2320-2890

DOI

10.1016/j.bj.2022.04.005

WoS UID

WOS:000997609900001