Phosphodiesterases 4 (PDE4) act as proinflammatory enzymes via degradation of cAMP, whereas PDE4 inhibitors play an anti-inflammatory role in vitro and in vivo. In particular, apremilast has been recently approved for the treatment of psoriasis and psoriatic arthritis. However, little is known on the expression pattern of PDE4 in psoriasis. We report that PDE4B and PDE4D mRNA are overexpressed in peripheral blood mononuclear cells (PBMC) from psoriasis, as compared with normal controls, while apremilast reduces PBMC production of a number of pro-inflammatory cytokines and increases the levels of anti-inflammatory mediators. PDE4 expression is up-regulated in psoriatic dermis as compared with normal skin, with particular regard to fibroblasts. This is confirmed in vitro, where both dermal fibroblasts (DF) and, to a greater extent, myofibroblasts (DM) express all PDE4 isoforms at the mRNA and protein level. Because PDE4 interacts with the nerve growth factor (NGF) receptor CD271 in lung fibroblasts, we evaluated the relationship and function of PDE4 and CD271 in normal human skin fibroblasts. All PDE4 isoforms co-immunoprecipitate with CD271 in DM, while apremilast inhibits apoptosis induced by β-amyloid, a CD271 ligand, in DM. Furthermore, apremilast significantly reduces NGF- and transforming growth factor-β1 (TGF-β1)-induced fibroblast migration, and inhibits DF differentiation into DM mediated by NGF or TGF-β1. Finally, in DM, apremilast significantly reduces cAMP degradation induced by treatment with β-amyloid. Taken together, these results indicate that PDE4 play an important role in psoriasis. In addition, the study reveals that the PDE4/CD271 complex could be important in modulating fibroblast functions.
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http://dx.doi.org/10.1016/j.cellsig.2016.01.007 | DOI Listing |
Front Immunol
December 2024
Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Italy.
Background: The phosphodiesterase 4 (PDE4) inhibitor apremilast downregulates the production of IL-23 and other pro-inflammatory cytokines involved in the pathogenesis of psoriatic arthritis (PsA).
Aim: To investigate the effects of apremilast on the production of cytokines by peripheral blood monocyte-derived macrophages, innate-like lymphocyte cells (ILCs), mucosal-associated invariant T (MAIT) cells, γδ T cells, natural killer (NK) cells, and NKT-like cells from patients with PsA manifesting different clinical responses to the treatment.
Methods: Peripheral blood samples were obtained from patients with PsA at baseline and after 1 and 4 months of apremilast therapy (n = 23) and 20 controls with osteoarthritis.
EBioMedicine
December 2024
Lübeck Institute of Experimental Dermatology, University of Lübeck, Lübeck, Germany; Department of Dermatology, University Hospital Schleswig-Holstein Lübeck, Lübeck, Germany; Institute and Comprehensive Centre for Inflammation Medicine, University-Hospital Schleswig-Holstein, Lübeck, Germany. Electronic address:
Background: Cardiovascular comorbidity increases morbidity and mortality in psoriasis. Systemic treatments, particularly biologics, are effective in alleviating skin and joint inflammation. Conversely, the impact of systemic therapy on cardiovascular disease risk and mortality in psoriasis remains uncertain.
View Article and Find Full Text PDFGeorgian Med News
September 2024
2Department of Pharmacology, College of Medicine, University of Baghdad, Iraq.
Aim: Current study was aimed to appraise the effectiveness and tolerability of apremilast in psoriasis patients at AL-Diwaniyah province, Iraq.
Materials And Methods: This prospective cross-sectional study conducted at Dermatology Unit/ AL-Diwaniyah Teaching Hospital/ Iraq, during the period from January to October 2023. A total of 125 patients, 90 males and 35 females, were enrolled in this study.
Eur Heart J Case Rep
November 2024
Department of Cardiology, University of Athens Medical School, Hippokration General Hospital, 114 Vasilissis Sofias Avenue, Athens 11527, Greece.
Background: Behçet's disease (BD) is a multisystemic chronic inflammatory disorder. Cardiac manifestations in BD are extremely rare. There have been no reports of cardiac involvement of BD and especially endomyocardial fibrosis in the left ventricle (LV).
View Article and Find Full Text PDFJ Dermatolog Treat
December 2024
Division of Dermatology, McMaster University, Hamilton, Canada.
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