PDE4

Full name: Phosphodiesterase 4

Size:1 50–125 kDa

Family:2 PDE4 isoenzyme subfamily (PDE4A to PDE4D) of the phosphodiesterase enzyme family

Major cellular sources:2,3 Neutrophils, T cells, macrophages, monocytes, eosinophils, DCs, NK cells, epithelial cells, keratinocytes, chondrocytes, and synoviocytes

Major cellular targets:3 Epithelial cells, such as those lining the airways

Disease states associated with:2,4 Asthma, chronic obstructive pulmonary disease, psoriasis, psoriatic arthritis, and Behçet’s disease

Major physiologic functions:

  • Each enzyme within the PDE4 family specifically targets cAMP for degradation and selectively hydrolyses cAMP into AMP, downstream controlling a network of pro-inflammatory and anti-inflammatory mediators.2,3

  • Inhibition of PDE4 increases the intracellular concentration of cAMP, which decreases the production of pro-inflammatory cytokines, such as TNF-α, IFN-γ, IL-2, IL-6, IL-17, IL-22, and IL-23, and increases the production of anti-inflammatory mediators, such as IL-10.3,5,6

  • PDE4 inhibition targets a central pathogenic process that bypasses complex antigen receptor–specific immunoregulatory mechanisms. Thus, selective PDE4 inhibition has been investigated for numerous autoimmune conditions, including ankylosing spondylitis, Alzheimer’s disease, psoriasis, psoriatic arthritis, sarcoidosis, systemic lupus erythematosus, inflammatory bowel disease, atopic dermatitis, rheumatoid arthritis, and multiple sclerosis.2

AMP: adenosine monophosphate; cAMP: cyclic AMP; DC: dendritic cell; IFN-γ: interferon gamma; IL: interleukin; NK: natural killer; TNF: tumor necrosis factor.

References:

  • 1.

    Kilanowska A, Ziółkowska A. Int J Mol Sci. 2020;21:8244.

  • 2.

    Kumar N, Goldminz AM, Kim N, Gottlieb AB. BMC Med. 2013;11:96.

  • 3.

    Schafer P. Biochem Pharmacol. 2012;83:1583-1590.

  • 4.

    Li H, Zuo J, Tang W. Front Pharmacol. 2018;9:1048.

  • 5.

    Pincelli C, Schafer PH, French LE, Augustin M, Krueger JG. J Drugs Dermatol. 2018;17:835-840.

  • 6.

    Schafer PH, Chen P, Fang L, Wang A, Chopra R. J Immunol Res. 2015;2015:906349.