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

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 adhesion between human umbilical vein endothelial cells (HUVECs) and THP-1 monocytes has yet to be investigated.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. Adhesion between HUVECs and THP-1 cells was assayed using green fluorescent dye.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 PPARα and IL-10 expression. siRNA-associated suppression of PPARδ and IL-10 attenuated the effects of CAP on cell adhesion between HUVECs and THP-1 cells and inflammatory responses. Further, PPARα siRNA mitigated CAP-mediated induction of IL-10 expression.These findings imply that CAP improves inflamed endothelial-monocyte adhesion via a PPAR/IL-10-dependent pathway. The current study provides in vitro evidence for a therapeutic approach for treating atherosclerosis.