Figure 1.

Pentoxifylline is able to dampen activation of two major proinflammatory signaling pathways (the NFκB and JAK-STAT) via antagonist effect on adenosine binding with its receptor (A_2AAR). Triggering A_2AAR causes elevation of intracellular cAMP levels. This leads to increase SUMO-1 activity along with inhibition of the E3 SCF Ub ligase complex, which prevents IκBα ubiquitination and degradation, thereby switching off the NFκB pathway. Moreover, high cAMP levels suppress cytokine-mediated JAK/STAT signaling via induction of the inhibitory protein SOCS3.