The effects of BRL-50481 on ovalbumin-induced asthmatic lung inflammation exacerbated by co-exposure to Asian sand dust in the murine model.
Hong Jo KimJin Yong SongTae Il ParkWon Seok ChoiJong Heon KimOh Seong KwonJi Yun LeePublished in: Archives of pharmacal research (2022)
Asian sand dust (ASD), which mainly originates in China and Mongolia in the spring and blows into Korea, can exacerbate respiratory and immunological diseases. This study aims to observe effects of co-exposure to ASD on ovalbumin (OVA)-induced asthmatic lung inflammation and of treatment with a phosphodiesterase 7 (PDE7) inhibitor in a mouse model. The challenge with OVA increased airway hyperresponsiveness (AHR) and inflammatory cell infiltration into the lung tissue. Interleukin (IL)-13, tumor necrosis factor-alpha, monocyte-protein-1, mucin, and antigen-specific IgE and IgG1 production increased in mouse serum. The co-exposure of ASD significantly exacerbated these effects in this asthma model. Notably, the administration of a PDE7 inhibitor, BRL-50481 (BRL), significantly reduced AHR, infiltration of inflammatory cells into the lungs, and the levels of type 2 T helper cell-related cytokines, antigen-specific immunoglobulins, and mucin. Thus, the administration of BRL ameliorated OVA-induced allergic asthmatic responses exacerbated by co-exposure to ASD. This study suggests that PDE7 inhibition can be a therapeutic strategy for inflammatory lung diseases and asthma via the regulation of T lymphocytes and reduction of IL-13, and, consequently, mucin production.
Keyphrases
- autism spectrum disorder
- oxidative stress
- diabetic rats
- lung function
- high glucose
- attention deficit hyperactivity disorder
- mouse model
- single cell
- induced apoptosis
- drug induced
- intellectual disability
- dendritic cells
- cell therapy
- allergic rhinitis
- rheumatoid arthritis
- endothelial cells
- drinking water
- stem cells
- immune response
- health risk
- polycyclic aromatic hydrocarbons
- bone marrow
- air pollution
- risk assessment
- peripheral blood
- small molecule
- cell death
- smoking cessation