Discover PsA

Discover the Role of PDE4 in Psoriatic Arthritis

Research is focused on understanding the broader inflammatory processes at work and the intracellular signaling pathways that are involved in the overproduction of a network of proinflammatory mediators

Fold image
corner image

This animation provides a simplified overview of how degradation of cyclic adenosine monophosphate (cAMP) by PDE4 modulates the production of pro- and anti-inflammatory mediators.32, 33, 34, 35

White fold
White rounded corner

Inflammation is Generally Viewed as Part of the Body's Normal Response to Injury or Infection36

However, an inflammatory response that is inappropriate (eg, in response to self-antigens), disproportionately severe, or inappropriately prolonged may become a problem in itself. Inflammatory responses are generally considered to be tightly regulated. Several regulatory mechanisms help to terminate responses to foreign antigens (to return the immune system to a basal state after the foreign antigen has been cleared) and to maintain unresponsiveness, or tolerance, to self-antigens. Thus, these regulatory mechanisms help to establish immune homeostasis.36

If these homeostatic mechanisms fail, activated immune cells may continue to proliferate, to release proinflammatory mediators, and to recruit more immune cells to the affected site, thus creating a chronic cycle of aberrant inflammation.36

Research is focused on understanding the broader inflammatory processes at work and the intracellular signaling pathways that are involved in the overproduction of a network of proinflammatory mediators. Phosphodiesterase 4 (PDE4) plays an important role in regulating these signaling pathways within immune cells.32 PDE4 degrades cyclic adenosine monophosphate (cAMP), a naturally occurring second messenger that is involved in intracellular communication.32, 37 Thus, PDE4 promotes production of proinflammatory mediators (eg, TNF-α, IL-17, and IFN-γ) and decreases production of anti-inflammatory mediators (eg, IL-10).32, 33, 34, 35 The presence of this network of proinflammatory mediators in joint-resident cells in the synovium is thought to account for the characteristic joint swelling and tenderness associated with PsA.38

Learn more about PDE4 and its role in Psoriatic Arthritis at DiscoverPDE4.com

Fold image
corner image

Receive Email Updates & Additional Information

Sign-up Now »
Fold image
corner image

References:

  • 32 Bäumer W, Hoppmann J, Rundfeldt C, Kietzmann M. Highly selective phosphodiesterase 4 inhibitors for the treatment of allergic skin diseases and psoriasis. Inflamm Allergy Drug Targets. 2007;6:17‑26.
  • 33 Souness JE, Griffin M, Maslen C, et al. Evidence that cyclic AMP phosphodiesterase inhibitors suppress TNF alpha generation from human monocytes by interacting with a 'low‑affinity' phosphodiesterase 4 conformer. Br J Pharmacol. 1996;118:649‑658.
  • 34 Ma R, Yang BY, Wu CY. A selective phosphodiesterase 4 (PDE4) inhibitor Zl‑n‑91 suppresses IL‑17 production by human memory Th17 cells. Int Immunopharmacol. 2008;8:1408‑1417.
  • 35 Oger S, Mehats C, Dallot E, et al. Evidence for a role of phosphodiesterase 4 in lipopolysaccharide‑stimulated prostaglandin E2 production and matrix metalloproteinase‑9 activity in human amniochorionic membranes. J Immunol. 2005;174:8082-8089.
  • 36 Van Parijs L, Abbas AK. Homeostasis and self‑tolerance in the immune system: turning lymphocytes off. Science. 1998;280:243‑248.
  • 37 Taskén K, Aandahl EM. Localized effects of cAMP mediated by distinct routes of protein kinase A. Physiol Rev. 2004;84:137‑167.
  • 38 van Kuijk AW, Reinders‑Blankert P, Smeets TJ, et al. Detailed analysis of the cell infiltrate and the expression of mediators of synovial inflammation and joint destruction in the synovium of patients with psoriatic arthritis: implications for treatment. Ann Rheum Dis. 2006;65:1551‑1557.
Fold image
corner image