Hwang Lakkyong, Jin Jun-Jang, Ko Il-Gyu, Kim Suyeon, Cho Young-A, Sung Jun-Seok, Choi Cheon Woong, Chang Bok Soon
Department of Physiology, College of Medicine, Kyung Hee University, Seoul, Korea.
Department of Medicine, Graduate School, Kyung Hee University, Seoul, Korea.
Int Neurourol J. 2021 May;25(Suppl 1):S19-26. doi: 10.5213/inj.2142168.084. Epub 2021 May 31.
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.
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 A2A receptor (A2AR), 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.
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 A2AR, but PDRN treatment more enhanced A2AR 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 A2AR.
PDRN treatment attenuated inflammation in the trachea of the PM10-exposed mice. This improving effect of PDRN can be ascribed to the activation of A2AR through the cAMP-PKA pathway.
吸入含有大量颗粒物（PM）的空气会引发多种呼吸系统疾病，包括哮喘、慢性阻塞性肺疾病和肺癌。本研究评估了在PM10暴露的气管炎症模型中，给予聚脱氧核糖核苷酸（PDRN）后炎症因子表达的变化。
将PM10注入小鼠气管以诱导急性炎症损伤，每日给予PDRN和3,7 - 二甲基 - 1 - 丙炔基黄嘌呤（DMPX），持续3天，观察炎症因子的变化。通过酶联免疫吸附测定、免疫荧光和蛋白质印迹分析检测炎症细胞因子、腺苷A2A受体（A2AR）、蛋白激酶A（PKA）、3′,5′ - 环磷酸腺苷反应元件结合蛋白（CREB）的表达。
暴露于PM的气管显示肿瘤坏死因子（TNF）-α和白细胞介素（IL）-1β表达增加，而PDRN治疗可抑制暴露于PM的小鼠中TNF-α和IL-1β的表达。暴露于PM的气管显示核因子（NF）-κB磷酸化增加，而PDRN治疗可抑制暴露于PM的小鼠中核因子 - κB的磷酸化。暴露于PM的气管显示A2AR表达增加，但PDRN治疗可进一步增强暴露于PM的小鼠中A2AR的表达。PKA磷酸化未发生变化，CREP磷酸化降低，然而PDRN治疗可增加暴露于PM的小鼠中PKA和CREB的磷酸化。DMPX治疗可阻断PDRN对暴露于PM的小鼠的所有作用，表明PDRN的作用是通过A2AR发生的。
PDRN治疗减轻了暴露于PM10的小鼠气管中的炎症。PDRN的这种改善作用可归因于通过cAMP - PKA途径激活A2AR。
