Attenuation effect of polydeoxyribonucleotide on inflammatory cytokines and apoptotic factors induced by particulate matter (PM10) damage in human bronchial cells.
Lakkyong HwangIl Gyu KoJun-Jang JinSang-Hoon KimYong-Seok JeeJae Joon HwangCheon Woong ChoiBok Soon ChangPublished in: Journal of biochemical and molecular toxicology (2020)
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.
Keyphrases
- particulate matter
- cell death
- cell cycle arrest
- air pollution
- induced apoptosis
- oxidative stress
- endoplasmic reticulum stress
- anti inflammatory
- polycyclic aromatic hydrocarbons
- heavy metals
- endothelial cells
- signaling pathway
- cell proliferation
- rheumatoid arthritis
- gene expression
- water soluble
- stem cells
- high throughput
- induced pluripotent stem cells
- south africa
- high glucose
- cell therapy
- human health