Chronic airway inflammation and airway remodeling are the major pathophysiological characteristics of chronic obstructive pulmonary disease (COPD). Resveratrol and genistein have been previously demonstrated to have anti‑inflammatory and antioxidative properties. The present study aimed to measure the inhibitory effects of resveratrol and genistein on tumor necrosis factor (TNF)‑α and matrix metalloproteinase (MMP)‑9 concentration in patients with COPD. Lymphocytes were isolated from the blood of 34 patients with COPD and 30 healthy subjects, then randomly divided into the following four treatment groups: Control, dexamethasone (0.5 µmol/l), resveratrol (12.5 µmol/l) and genistein (25 µmol/l) groups. After 1 h of treatment, 100 µl lymphocytes were collected for nuclear factor (NF)‑κB immunocytochemical staining. After 48 h treatment, the supernatant of the lymphocytes was collected for analysis of TNF‑α and MMP‑9 concentration levels. The percentage of lymphocytes with positive nuclear NF‑κB expression was analyzed by immunocytochemical staining. The concentration levels of TNF‑α and MMP‑9 were measured using radioimmunoassay and enzyme‑linked immunosorbent assay, respectively. The present study demonstrated that the percentage of NF‑κB‑positive cells, and the levels of TNF‑α and MMP‑9 in lymphocytes from patients with COPD patients were significantly higher compared with healthy subjects. Additionally, there were positive correlations between the percentage of NF‑κB‑positive cells, and the concentration levels of TNF‑α and MMP‑9 in patients with COPD. All three factors were significantly reduced in lymphocytes treated with resveratrol and genistein, and the inhibitory effects of resveratrol on NF‑κB, TNF‑α and MMP‑9 were more potent than the effects of genistein. In conclusion, resveratrol and genistein may inhibit the NF‑κB, TNF‑α and MMP‑9‑associated pathways in patients with COPD. It is suggested that resveratrol and genistein may be potential drugs candidates for use in the treatment of COPD.

The adverse effects of polluted air on human health have been increasingly appreciated worldwide. It is estimated that outdoor air pollution is associated with the death of 4.2 million people globally each year. Accumulating epidemiological studies indicate that exposure to ambient fine particulate matter (PM_2.5), one of the important air pollutants, significantly contributes to respiratory mortality and morbidity. PM_2.5 causes lung damage mainly by inducing inflammatory response and oxidative stress. In this paper, we reviewed the research results of our group on the effects of PM_2.5 on chronic obstructive pulmonary disease, asthma, and lung cancer. And recent research progress on epidemiological studies and potential mechanisms were also discussed. Reducing air pollution, although remaining a major challenge, is the best and most effective way to prevent the onset and progression of respiratory diseases.

Chronic obstructive pulmonary disease (COPD) is characterized by accelerated lung aging. Smoking is the critical risk factor for COPD. Cellular senescence of airway epithelial cells is the cytological basis of accelerated lung aging in COPD, and the regulation of microRNAs (miRNAs) is the central epigenetic mechanism of cellular senescence. Resveratrol (Res) is a polyphenol with anti-aging properties. This study investigated whether Res attenuates cigarette smoke extract (CSE)-induced cellular senescence in human airway epithelial cells (BEAS-2B) through the miR-34a/SIRT1/nuclear factor-kappaB (NF-κB) pathway. BEAS-2B cells were treated with Res, CSE and transfected with miR-34a-5p mimics. Cellular senescence was evaluated by senescence -related β-galactosidase (SA-β-gal) staining and expression of senescence-related genes (p16, p21, and p53). The expressions of miR-34a-5p, SIRT1, and NF-κB p65 were examined using quantitative real time polymerase chain reaction and western blotting. The senescence-associated secretory phenotype (SASP) cytokines (IL-1β, IL-6, IL-8, TNF-α) were assessed by enzyme-linked immunosorbent assay. The binding between miR-34a-5p and SIRT1 was confirmed by dual-luciferase reporter assay. The results showed that CSE dose-dependently decreased cell viability and elevated cellular senescence, characterized by increased SA-β-gal staining and senescence-related gene expressions (p16, p21, and p53). Further, CSE dose-dependently increased the expression of miR-34a-5p and SASP cytokines (IL-1β, IL-6, IL-8, TNF-α) in BEAS-2B cells. Pretreatment with Res inhibited CSE-induced cellular senescence and secretion of SASP cytokines (IL-1β, IL-6, IL-8, TNF-α) in a dose-dependent manner. Moreover, Res reversed the CSE-induced down-regulation of SIRT1 and up-regulation of miR-34a-5p and NF-κB p65. SIRT1 is a target of miR-34a-5p. Overexpression of miR-34a-5p via transfection with miR-34a-5p mimic in BEAS-2B cells attenuated the inhibitory effect of Res on cellular senescence, accompanied by reversing the expression of SIRT1 and NF-κB p65. In conclusion, Res attenuated CSE-induced cellular senescence in BEAS-2B cells by regulating the miR-34a/SIRT1/NF-κB pathway, which may provide a new approach for COPD treatment.

Background: Airway epithelial cells (AECs) and alveolar macrophages are involved in airway inflammation. The direct effects of atmospheric fine-particulate-matter (PM2.5) on airway cells, such as AECs and alveolar macrophages, have been widely investigated, but the effect of cell-cell interaction on inflammatory response remains unclear. Exosomes play a crucial role in intercellular communication. However, the cellular interaction of exosomes in PM2.5-induced airway inflammation is unclear. Methods: The PM2.5-induced human bronchial epithelial (BEAS-2B) cells and phorbol 12-myristate 13-acetate-induced macrophages (M&phis;) were co-cultured and then the expression of IL-6, IL-1β, TNF-α and miRNA-155-5p were detected. Exosomes from PM2.5-exposed BEAS-2B cells were then co-cultured with M&phis; to detect the expression of miR-155-5p and inflammatory cytokines, as well as cytokine signaling inhibitor-1 (SOCS1)/NFκB, and to detect the effect of the exosome inhibitor GW4869. Results: After the co-culture of PM2.5-induced BEAS-2B cells and M&phis;, the expression of M&phis;-derived IL-6, IL-1β, and TNF-α, as well as miRNA-155-5p were upregulated. The expression of miRNA-155-5p was upregulated in BEAS-2B and BEAS-2B cell-derived exosomes after exposure to PM2.5. Furthermore, co-culturing exosomes derived from PM2.5-exposed BEAS-2B cells with M&phis;, upregulated miR-155-5p and inflammatory cytokines, decreased cytokine signaling inhibitor-1 (SOCS1) expression, and activated NF-κB. In addition, adding exosome inhibitor GW4869 to PM2.5-interfered BEAS-2B cells co-culture with M&phis; downregulated miRNA-155-5p expression, inhibited NF-κB, and reduced the levels of inflammatory factors. Conclusion: PM2.5 promotes M&phis; inflammation by upregulating miRNA-155-5P in exosomes obtained from BEAS-2B cells through miR-155-5P/SOCS1/NF-κB pathway. Exosomal miRNAs mediate cellular communication between BEAS-2B cells and M&phis;, which may be a new mechanism of PM2.5-stimulated pulmonary inflammatory response.