Resveratrol induces cell cycle arrest and apoptosis in human eosinophils from asthmatic individuals

Abstract

Abstract. Eosinophils exert a number of inflammatory effects through the degranulation and release of intracellular mediators, and are considered to be key effector cells in allergic disorders, including asthma. In order to investigate the regulatory effects of the natural polyphenol, resveratrol, on eosinophils derived from asthmatic individuals, the cell counting Kit-8 assay and flow cytometry analysis were used to determine cell proliferation and cell cycle progression in these cells, respectively. Cellular apoptosis was detected using annexin V-fluorescein isothiocyanate/propidium iodide double-staining. The protein expression levels of p53, p21, cyclin-dependent kinase 2 (CDK2), cyclin A, cyclin E, Bim, B-cell lymphoma (Bcl)-2 and Bcl-2-associated X protein (Bax) were measured by western blot analysis following resveratrol treatment. The results indicated that resveratrol effectively suppressed the proliferation of eosinophils from asthmatic patients in a concentration-and time-dependent manner. In addition, resveratrol was observed to arrest cell cycle progression in G 1 /S phase by increasing the protein expression levels of p53 and p21, and concurrently reducing the protein expression levels of CDK2, cyclin A and cyclin E. Furthermore, resveratrol treatment significantly induced apoptosis in eosinophils, likely through the upregulation of Bim and Bax protein expression levels and the downregulation of Bcl-2 protein expression. These findings suggested that resveratrol may be a potential agent for the treatment of asthma by decreasing the number of eosinophils.

Cellular and Molecular Targets of Resveratrol on Lymphoma and Leukemia Cells

“…These data are strengthened by recent evidences demonstrating that eosinophils undergo cell cycle arrest and apoptosis following RSV treatment [ 29 ]. When treated with RSV, eosinophils from asthmatic individuals show an increase in the protein levels of p53 and p21 and, concurrently, reduced protein levels of Cdk2, cyclin A and cyclin E. Apoptosis was induced through the increase in the apoptotic mediators Bim and Bax and the downregulation of Bcl2 [ 29 ].…”

Different Biological Pathways Between Good and Poor Inhaled Corticosteroid Responses in Asthma

“…Since long time ago, we have known that dexamethasone induces irreversible G1 arrest and death of a human lymphoid cell line (30). An arrest of cell cycle progression in the G1/S phase also induced apoptosis of human eosinophils from patients with asthma (31). All these together imply a potential role of the G1/S transition in blood cells in response to corticosteroids.…”

Effects of chemokine receptor 3 gene silencing by RNA interference on eosinophils

“…As important processes in the development of allergic diseases, promoting the apoptosis of EOS and reducing the infiltration of EOS into local tissues could potentially relieve local inflammation in allergic diseases (7). IL-3, IL-5 and GM-CSF can promote the survival of EOS (23).…”

“…To date there is no cure for AR, therefore, further research is required. Recent studies have demonstrated that eosinophils (EOS) are the primary effector cells in AR, and the localization and activation of a large number of EOS is an important feature of allergic diseases (7–10). Due to the signaling link between the nasal cavity and bone marrow, a large number of EOS are stimulated by allergens that infiltrate local tissues (11).…”