Journal article

Publication year: 2022

Pages: 237-246

Journal: Journal of the European Academy of Dermatology and Venereology

Volume number: 36

Issue number: 2

ISSN: 0926-9959

eISSN: 1468-3083

Open access status: Hybrid

DOI Link: https://doi.org/10.1111/jdv.17769

Publisher: Wiley

Abstract: 
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 TNF alpha-activated endothelial cells. Methods Human umbilical vein endothelial cells (HUVEC) were treated with tumour necrosis factor-alpha (TNF alpha) 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 TNF alpha-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 TNF alpha. Mechanistically, apremilast suppressed activation of nuclear factor kappa B (NF kappa B) and mitogen-activated protein kinases (MAPK) signalling in activated HUVECs. Furthermore, inhibition of p38, C-Jun-N-terminale Kinase (JNK) and NF kappa B 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.

Harvard Citation style: Otto, M., Dorn, B., Grasmik, T., Doll, M., Meissner, M., Jakob, T., et al. (2022) Apremilast effectively inhibits TNFα-induced vascular inflammation in human endothelial cells, Journal of the European Academy of Dermatology and Venereology, 36(2), pp. 237-246. https://doi.org/10.1111/jdv.17769

APA Citation style: Otto, M., Dorn, B., Grasmik, T., Doll, M., Meissner, M., Jakob, T., & Hrgovic, I. (2022). Apremilast effectively inhibits TNFα-induced vascular inflammation in human endothelial cells. Journal of the European Academy of Dermatology and Venereology. 36(2), 237-246. https://doi.org/10.1111/jdv.17769