Phosphodiesterase 4 in inflammatory diseases: Effects of apremilast in psoriatic blood and in dermal myofibroblasts through the PDE4/CD271 complex

Cellular Signalling
Peter SchaferCarlo Pincelli

Abstract

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. F...Continue Reading

References

Feb 12, 1998·Biochimica Et Biophysica Acta·R ObernolteE R Shelton
Jan 13, 2004·Physiological Reviews·Kjetil Taskén, Einar Martin Aandahl
Nov 1, 2005·Drug Discovery Today·Miles D HouslayKam Y J Zhang
Jul 18, 2006·The Journal of Investigative Dermatology·Vladimir A BotchkarevCarlo Pincelli
Aug 24, 2007·Expert Opinion on Investigational Drugs·Ali KeshavarzianAli Banan
Apr 20, 2011·Journal of Cellular Physiology·Elisabetta PalazzoCarlo Pincelli
Apr 14, 2015·Expert Opinion on Pharmacotherapy·Hunar AbdulrahimAlvin Wells

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Citations

Oct 5, 2016·Scientific Reports·Hiroki TanigawaYuichi Oike
Sep 22, 2018·American Journal of Physiology. Heart and Circulatory Physiology·Arantxa Barandiarán AizpuruaVanessa van Empel
Oct 24, 2018·International Journal of Dermatology·Anna Michalska-BańkowskaPiotr Michalski
Nov 22, 2019·Modern Rheumatology·Mitsuhiro Takeno
Feb 15, 2020·Expert Opinion on Pharmacotherapy·Francesco CasoLuisa Costa
Jan 22, 2020·American Journal of Physiology. Renal Physiology·Man XuZhanjun Jia
May 21, 2020·Journal of Clinical Pharmacology·Vivek PurohitWilliam C Ports
Apr 27, 2020·Journal of the European Academy of Dermatology and Venereology : JEADV·Ayman Abdelmaksoud, Mohamad Goldust
Mar 23, 2017·Frontiers in Medicine·Carlo Pincelli
Aug 2, 2017·International Urology and Nephrology·Honglin DingYili Liu
Oct 18, 2018·Experimental Dermatology·Emma Guttman-YasskyMichael A Zielinski
Feb 19, 2017·Drugs·Gillian M Keating
Dec 12, 2018·The Journal of Dermatology·Susumu IchiyamaHidehisa Saeki
Aug 18, 2020·International Journal of General Medicine·Solmaz Ohadian Moghadam
Nov 6, 2018·Frontiers in Pharmacology·Heng LiWei Tang
Jun 18, 2019·Therapeutic Advances in Gastroenterology·João SabinoMarc Ferrante
Nov 10, 2020·Indian Journal of Dermatology·Abhishek DeAarti Sarda
Jan 12, 2020·Pharmacology & Therapeutics·Claire LugnierBernard Geny
Mar 5, 2021·Pharmacology & Therapeutics·Xiaoliang YangKenji Kabashima
Jun 18, 2021·European Journal of Pharmacology·Natsuki Kubota-IshidaYuji Tabata
Jul 9, 2021·Regulatory Toxicology and Pharmacology : RTP·Teresa WegesserSheroy Minocherhomji
Oct 27, 2021·Journal of the European Academy of Dermatology and Venereology : JEADV·M OttoI Hrgovic

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