Step inside the Control Center

The role of phosphodiesterase-4 (PDE4)
in psoriatic inflammation

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Explore the Complexities

PSORIATIC DISEASE IS COMPLICATED¹

The etiology of psoriasis is complex and is based on an intricate relationship between environmental and genetic influences that paves the way for disease-initiating events^1-3

A cascade of events driven by pro-inflammatory and anti-inflammatory cytokines is believed to control the inflammation process linked to psoriatic disease^1,4

THE COMPLICATED NETWORKING OF INTERLEUKINS
IS NOT FULLY UNDERSTOOD^4,7,11

Inflammation is caused by a complicated interplay of cytokine signaling¹¹

Many cytokines (small proteins that affect the interactions and communication between cells) are involved in the inflammatory cascade^7,12
There may not be a single or key cytokine responsible for psoriatic disease^12,13
The complicated networking of interleukins is not fully understood^4,7,11

A neon red oval shape with the text "PDE4" inside an octagon and more text "Click to dive into the inflammatory cell", along will "anti-inflammatory mediators" and "pro-inflammatory mediators" on the outside

ANTI-INFLAMMATORY
MEDIATORS

PRO-INFLAMMATORY
MEDIATORS

CLICK TO DIVE INTO
PRO-INFLAMMATORY CELLS

ROLE OF PDEs

cAMP is a key secondary messenger for a variety of inflammatory mediators, and PDEs regulate their intensity, duration, and signaling pathways within immune cells^14-16

cAMP is important to the immune system because it mitigates pro-inflammatory cell functions and acts as a secondary messenger in cell signaling for inflammatory mediators and cytokines^14-16
There are 11 distinct PDE families with differing specificity; among these, PDE4 is responsible for degrading cAMP to AMP^14,17,18
PDE4 is a cAMP-specific PDE that has been shown to degrade cAMP to AMP. Through PDE4 activity, cAMP levels drive the production of pro and anti-inflammatory mediators^14,15,19

PDE4 is essential for converting cAMP to AMP within the pro-inflammatory cells^14,16

PDE4 is expressed by monocytes and DCs, both of which exhibit multiple functions during immune responses¹⁶

Graphics that represent PDE4 activity in monocytes and DCs, both of which exhibit multiple functions during immune responses

PDE4 and
Immune Cells

PDE4 is present in both circulating and activated pro-inflammatory cells of the immune system^16,20

PDE4 is predominant within monocytes, dendritic cells, eosinophils, neutrophils, macrophages, and T cells²⁰
PDE4 is also expressed in non-immune cells, such as keratinocytes, fibroblasts, and chondrocytes^20,21

CLINICAL PERSPECTIVE ON THE
PDE4 PATHWAY IN PsO

PRESENTED BY BRUCE STROBER, MD, PhD

CLINICAL PERSPECTIVE ON THE
PDE4 PATHWAY IN PsA

PRESENTED BY PHILIP MEASE, MD

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PSORIATIC DISEASE IS COMPLICATED1

The etiology of psoriasis is complex and is based on an intricate relationship between environmental and genetic influences that paves the way for disease-initiating events1-3

Inflammation is caused by a complicated interplay of cytokine signaling11

ROLE OF PDEs

cAMP is a key secondary messenger for a variety of inflammatory mediators, and PDEs regulate their intensity, duration, and signaling pathways within immune cells14-16

PDE4 and Immune Cells

PDE4 is present in both circulating and activated pro-inflammatory cells of the immune system16,20

CLINICAL PERSPECTIVE ON THE PDE4 PATHWAY IN PsO

CLINICAL PERSPECTIVE ON THE PDE4 PATHWAY IN PsA

ROLE OF PDE4 IN PRO-INFLAMMATORY CELLS