Attenuation effect of polydeoxyribonucleotide on inflammatory cytokines and apoptotic factors induced by particulate matter (PM10) damage in human bronchial cells

Abstract

Particulate matter (PM) of 10‐μm‐sized fine dust in the air penetrates the respiratory tract and contributes to the increasing incidence of various lung diseases, but its definite mechanism is not known. Recently, polydeoxyribonucleotide (PDRN) has been shown to have anti‐inflammatory and regenerative effects in various tissues. However, the bronchial‐related mechanism is not well‐understood. Hence, this experiment is intended to demonstrate the beneficial effect of PDRN administration on PM10‐induced injury in human bronchial‐derived NCI‐H358 cells. To confirm the protective effect of PDRN, PM10 was applied after PDRN pretreatment to confirm changes in NCI‐H358 cells. Experiments were conducted to measure cell survival, cytotoxicity, inflammation, and apoptotic factor changes. WST‐8 assay was used to confirm cell viability, and lactate dehydrogenase assay was used to obtain cytotoxicity. In addition, changes in inflammatory cytokines and apoptotic factors were confirmed by enzyme‐linked immunosorbent assay and Western blot. Decreased cell viability and increased cytotoxicity, inflammatory cytokines, and apoptotic factors were observed after exposure to PM10. However, pretreatment with PDRN enhanced cell viability and reduced cytotoxicity. In addition, the expression of inflammatory cytokines such as tumor necrosis factor‐α, interleukin‐6 (IL‐6), and IL‐1β, and cell death factors such as Apaf‐1, cyt c, caspase‐3, caspase‐9, Bid, and Bax/Bcl‐2 ratio were decreased by PDRN administration in PM10‐exposed NCI‐H358 cells. PDRN, an A2AR agonist, affects cAMP activation and regulation of phosphorylation of PKA and CREB. In addition, treatment with A2AR antagonist 3,7‐dimethyl‐1‐propargylxanthine significantly blocked PDRN's effect. These anti‐cytotoxicity, anti‐inflammation, and anti‐apoptosis effects of PDRN can be attributed to the adenosine A2AR enhancing effect on PM10‐exposed bronchial cells.

Duchesnea indica Extract Attenuates Coal Fly Ash-Induced Inflammation in Murine Alveolar Macrophages through the NF-Kappa B Pathway

“…Nanoparticles can retain for a long period of time in the atmosphere and easily move in the air. Chronic exposures of CFA can cause accumulation of sediments in the lungs and lead to serious adverse effects, such as inflammation in the alveolar cells [ 3 , 4 ]. Moreover, nanoparticles are responsible for many respiratory diseases, such as asthma, bronchitis, chronic obstructive pulmonary diseases (COPD), and lung carcinoma [ 5 ].…”

Applications of Marine Organism-Derived Polydeoxyribonucleotide: Its Potential in Biomedical Engineering

“…One study revealed that Ok-PDRN has anti-apoptotic and anti-inflammatory effects in human bronchial cells stimulated with 10-μm-sized particulate matter (PM) (fine dust) [ 16 ]. Ok-PDRN (0–8 μg/mL) ameliorated PM10-induced apoptosis without cytotoxicity on human bronchial cells and suppressed the production of inflammatory cytokines [interleukin (IL)-1β, IL-6, and tumor necrosis factor-α (TNF-α)] and apoptotic factors (caspase-3 and -9).…”

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

“…Activation of PKA enhanced phosphorylation of CREB, which led to the nuclear localization and activation of CREB [30]. Phosphorylation of CREB exerted anti-inflammatory effect [10,11] and improved short-term memory [31]. In the cur-rent study, PM-exposed trachea showed PKA phosphorylation was not changed and CREP phosphorylation was decreased, however PDRN treatment increased phosphorylation of PKA and CREB in PM-exposed mice.…”

“…It is well known that PM aspiration increases inflammatory factors and accelerates apoptotic cell death [2][3][4]6]. Reduced cell viability and production of TNF-α, IL-1β, and IL-6 were observed after exposure to PM10 in human bronchial-derived NCI-H358 cells [11]. Since the PM composition in the air has a high content of heavy metals and transition metals, its toxicity may cause damage to the human body [17,18].…”

“…One of the adenosine agonists, polydeoxyribonucleotide (PDRN) is known as a candidate for anti-inflammatory drugs by inhibiting inflammation and apoptosis by selectively stimulating A2AR in lung-injured animals. PDRN is derived from salmon semen and consists of a stable mixture of nucleotides ranging in size from 50 to 1,500 kDa [10,11]. Of the 4 adenosine receptors, PDRN selectively acts on A2AR, and selective stimulation of A2AR effectively inhibits inflammatory substances [10][11][12].…”