Polydeoxyribonucleotide Attenuates Airway Inflammation Through A2AR Signaling Pathway in PM10-Exposed Mice

Abstract

Purpose: Inhalation of air containing high amounts of particular matter (PM) causes various respiratory disorders including asthma, chronic obstructive pulmonary disease, and lung cancer. The changes of expression of inflammatory factors by polydeoxyribonucleotide (PDRN) administration in the PM10-exposed trachea inflammation model were evaluated.Methods: PM<sub>10</sub> was administered to mouse trachea to induce acute inflammatory damage, and changes in inflammatory factors were observed after administration of PDRN and 3,7-dimethyl-1-propargylxanthine (DMPX) for 3 days daily. Expression of inflammatory cytokines, adenosine A<sub>2A</sub> receptor (A<sub>2A</sub>R), protein kinase A (PKA), 3΄,5΄-cyclic adenosine monophosphate responsive element binding protein (CREB) were detected by enzyme‐linked immunosorbent assay, immunofluorescence, and western blot assay.Results: PM-exposed trachea showed increased tumor necrosis factor (TNF)-α and interleukin (IL)-1β expression, and expression of TNF-α and IL-1β was inhibited by PDRN treatment in PM-exposed mice. PM-exposed trachea showed increased nuclear factor (NF)-κB phosphorylation, and phosphorylation of nuclear factor-kappa B was inhibited by PDRN treatment in PM-exposed mice. PM-exposed trachea showed increased expression of A<sub>2A</sub>R, but PDRN treatment more enhanced A<sub>2A</sub>R expression in PM-exposed mice. PKA phosphorylation was not changed and CREP phosphorylation was decreased, however PDRN treatment increased phosphorylation of PKA and CREB in PM-exposed mice. DMPX treatment blocked all the effects of PDRN on PM-exposed mice, demonstrating that the action of PDRN occurs via A<sub>2A</sub>R.Conclusions: PDRN treatment attenuated inflammation in the trachea of the PM<sub>10</sub>-exposed mice. This improving effect of PDRN can be ascribed to the activation of A<sub>2A</sub>R through the cAMP-PKA pathway.

E prostanoid receptor‐3 promotes oxidized low‐density lipoprotein‐induced human aortic smooth muscle cells inflammation

“…On the other hand, some pro‐inflammatory agents (IL‐8, TNF‐α, IL‐6, IL‐17, IL‐1β, and ICAM‐1) were found to be modulated by EP3 in this research. As we know, CREB could mediate the pro‐inflammatory cytokines 43,44 . Thus, it can be concluded that EP3 promoted the inflammatory responses through up‐regulation of CREB.…”

“…As we know, CREB could mediate the pro‐inflammatory cytokines. 43 , 44 Thus, it can be concluded that EP3 promoted the inflammatory responses through up‐regulation of CREB.…”

Beneficial Effects of Polydeoxyribonucleotide (PDRN) in an In Vitro Model of Fuchs Endothelial Corneal Dystrophy

“…Previous papers have demonstrated that adenosine A 2Ar activation prevents ROS generation, also reducing inflammation and the apoptotic process [24,25]. PDRN, which is recognized as an A 2Ar agonist, showed several properties-including antioxidant, anti-apoptotic and anti-inflammatory ones-in several pre-clinical in vivo disease models, such as airway inflammation, cerebral ischemia, interstitial cystitis, acute lung injury, and ischemic colitis [26][27][28][29][30]. Moreover, a previous clinical trial demonstrated that PDRN eye drops stimulated corneal epithelium regeneration, thus supporting the hypothesis that it could be used for the treatment of corneal diseases [15,18].…”

Protective Properties of Intestinal Alkaline Phosphatase Supplementation on the Intestinal Barrier: Interactions and Effects

“…28 Intracellular cAMP levels are regulated by the state of adenosine bound to A 2A R. 29 PKA activation and PKA-mediated protein phosphorylation by cAMP form the cAMP−PKA signaling pathway, which further inhibits the activation of the NF-κB pathway. 30,31 Zuo et al found that, following the activation of the sympathetic nervous system in rats after stroke, adrenaline activated the expression of cAMP, PKA levels increased, and the NF-κB pathway was inhibited. 32…”