Int Neurourol J.  2021 May;25(Suppl 1):S19-26. 10.5213/inj.2142168.084.

Polydeoxyribonucleotide Attenuates Airway Inflammation Through A_2AR Signaling Pathway in PM₁₀-Exposed Mice

• Hwang L
• Jin JJ
• Ko IG
• Kim S
• Cho YA
• Sung JS
• Choi CW
• Chang BS

• KMID: 2516589
• DOI: http://doi.org/10.5213/inj.2142168.084

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
PM₁₀ 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_2A receptor (A_2AR), 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_2AR, but PDRN treatment more enhanced A_2AR 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_2AR.
Conclusions
PDRN treatment attenuated inflammation in the trachea of the PM₁₀-exposed mice. This improving effect of PDRN can be ascribed to the activation of A_2AR through the cAMP-PKA pathway.

Keyword

Particulate matter; Polydeoxyribonucleotide; Adenosine A2A receptor; Inflammation