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Updated: Oct 15, 2025
On-Chip Endothelial Inflammatory Phenotyping
Published on: July 21, 2012
Apremilast effectively inhibits TNFα-induced vascular inflammation in human endothelial cells
1Department of Dermatology and Allergy, Experimental Dermatology and Allergy Research Group, University Medical Center Giessen, Justus Liebig University Giessen, Giessen, Germany.
Background:
Patients with chronic inflammatory diseases (e.g. psoriasis and rheumatoid arthritis) are at increased risk for the development of atherosclerosis and cardiovascular diseases (CVD). Previous studies have suggested that phosphodiesterase 4 (PDE4) inhibitors possess anti-inflammatory properties.
Objectives:
Here we examined the effect of the PDE4 inhibitor apremilast, a well-established anti-psoriatic drug, on pro-inflammatory responses in TNFα-activated endothelial cells.
Methods:
Human umbilical vein endothelial cells (HUVEC) were treated with tumour necrosis factor-α (TNFα) in the presence or absence of apremilast. Expression levels of pro-inflammatory cytokines, chemokines and adhesion molecules were assessed by ELISA, western blot and RT-PCR. Effects of apremilast on adhesion and transendothelial migration (TEM) of THP-1 monocytic cells were analysed in transwell assays.
Results:
Apremilast suppressed TNFα-induced expression and secretion of important endothelial and monocytic pro-inflammatory factors, including granulocyte-macrophage colony-stimulating factor (GM-CSF), C-X-C motif chemokine ligand 10 (CXCL10), chemokine (C-C motif) ligand 2 (CCL2), vascular cell adhesion molecule 1 (VCAM-1), E-selectin and matrix metalloproteinase-9 (MMP9). Functionally, apremilast reduced adhesion of THP-1 cells to activated HUVECs and TEM in response to TNFα. Mechanistically, apremilast suppressed activation of nuclear factor κB (NFκB) and mitogen-activated protein kinases (MAPK) signalling in activated HUVECs. Furthermore, inhibition of p38, C-Jun-N-terminale Kinase (JNK) and NFκB in activated HUVECs decreased expression of GM-CSF, VCAM-1 and E-selectin. Additionally, apremilast decreased IL-17A-induced secretion of IL-6 and CCL2.
Conclusions:
We demonstrate that apremilast has distinct anti-inflammatory effects in activated HUVECs, indicating that apremilast could have the therapeutic potential to prevent higher risk for CVD in patients with chronic inflammatory diseases.
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