Doxofylline does not increase formoterol-induced cAMP nor MKP-1 expression in ASM cells resulting in lack of anti-inflammatory effect

Doxofylline is not just another theophylline!

“…However, it has also been shown that doxofylline, similarly to theophylline, has no effect on formoterol-induced cAMP production (consistent with these drugs not really being significant PDE inhibitors at sensible concentrations) and does not augment formoterol-induced upregulation of the anti-inflammatory protein, mitogen-activated protein kinase phosphatase 1 (MKP-1), in ASM cells. 26 Using human peripheral blood eosinophils isolated from asthma patients, Zhou et al 27 documented that doxofylline could effectively decrease the open probability of the calcium-activated potassium channels as a result of both the shortening of the open period and the prolongation of the close time. Intriguingly, doxofylline differs from other methylxanthines in its inability to antagonize calcium-activated potassium channels known to be the sites for calcium channel blockers and thus does not interfere with the influx of calcium into cells, or mobilize intracellular calcium stores.…”

“…31 Interestingly, there is evidence that unlike theophylline, doxofylline does not inhibit tumor necrosis factor-induced interleukin (IL)-8 secretion in ASM cells. 26 …”

Chemokines in COPD: From Implication to Therapeutic Use

“…This production could stimulate the airway epithelium, leading to its contraction and an increased permeability to inflammatory cells [100]. Of note, CXCL8 is also thought to be produced by lung fibroblasts when stimulated by epithelial cell-derived IL-1α [61] but also by bronchial smooth muscle cells [62] (Figure 2). Some studies have been conducted on mice models and have found that the mouse equivalent of CXCL8 (keratinocyte-derived chemokine) is also increased in the lungs of mice exposed to cigarette smoke extracts (CSE) [101].…”