{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T15:25:05Z","timestamp":1792855505150,"version":"4.5.0"},"reference-count":30,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2021,11,13]],"date-time":"2021-11-13T00:00:00Z","timestamp":1636761600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Acad Dermatol Venereol"],"published-print":{"date-parts":[[2022,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>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\u2010inflammatory properties.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objectives<\/jats:title><jats:p>Here we examined the effect of the PDE4 inhibitor apremilast, a well\u2010established anti\u2010psoriatic drug, on pro\u2010inflammatory responses in TNF\u03b1\u2010activated endothelial cells.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Human umbilical vein endothelial cells (HUVEC) were treated with tumour necrosis factor\u2010\u03b1 (TNF\u03b1) in the presence or absence of apremilast. Expression levels of pro\u2010inflammatory cytokines, chemokines and adhesion molecules were assessed by ELISA, western blot and RT\u2010PCR. Effects of apremilast on adhesion and transendothelial migration (TEM) of THP\u20101 monocytic cells were analysed in transwell assays.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Apremilast suppressed TNF\u03b1\u2010induced expression and secretion of important endothelial and monocytic pro\u2010inflammatory factors, including granulocyte\u2010macrophage colony\u2010stimulating factor (GM\u2010CSF), C\u2010X\u2010C motif chemokine ligand 10 (CXCL10), chemokine (C\u2010C motif) ligand 2 (CCL2), vascular cell adhesion molecule 1 (VCAM\u20101), E\u2010selectin and matrix metalloproteinase\u20109 (MMP9). Functionally, apremilast reduced adhesion of THP\u20101 cells to activated HUVECs and TEM in response to TNF\u03b1. Mechanistically, apremilast suppressed activation of nuclear factor \u03baB (NF\u03baB) and mitogen\u2010activated protein kinases (MAPK) signalling in activated HUVECs. Furthermore, inhibition of p38, C\u2010Jun\u2010N\u2010terminale Kinase (JNK) and NF\u03baB in activated HUVECs decreased expression of GM\u2010CSF, VCAM\u20101 and E\u2010selectin. Additionally, apremilast decreased IL\u201017A\u2010induced secretion of IL\u20106 and CCL2.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>We demonstrate that apremilast has distinct anti\u2010inflammatory effects in activated HUVECs, indicating that apremilast could have the therapeutic potential to prevent higher risk for CVD in patients with chronic inflammatory diseases.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jdv.17769","type":"journal-article","created":{"date-parts":[[2021,10,26]],"date-time":"2021-10-26T16:50:56Z","timestamp":1635267056000},"page":"237-246","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":35,"title":["Apremilast effectively inhibits TNF\u03b1\u2010induced vascular inflammation in human endothelial cells"],"prefix":"10.1111","volume":"36","author":[{"given":"M.","family":"Otto","sequence":"first","affiliation":[{"name":"Department of Dermatology and Allergy Experimental Dermatology and Allergy Research Group University Medical Center Giessen Justus Liebig University Giessen Giessen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B.","family":"Dorn","sequence":"additional","affiliation":[{"name":"Department of Dermatology and Allergy Experimental Dermatology and Allergy Research Group University Medical Center Giessen Justus Liebig University Giessen Giessen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T.","family":"Grasmik","sequence":"additional","affiliation":[{"name":"Department of Dermatology and Allergy Experimental Dermatology and Allergy Research Group University Medical Center Giessen Justus Liebig University Giessen Giessen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Doll","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Venereology and Allergy Goethe University Frankfurt\/Main 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