The effects of BRL-50481 on ovalbumin-induced asthmatic lung inflammation exacerbated by co-exposure to Asian sand dust in the murine model.

Abstract

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.

• Authors: Hong Jo Kim, Jin Yong Song, Tae Il Park, Won Seok Choi, Jong Heon Kim, Oh Seong Kwon, Ji-Yun Lee
• Journal: Archives of pharmacal research (Arch Pharm Res) Vol. 45 Issue 1 Pg. 51-62 (Jan 2022) ISSN: 1976-3786 [Electronic] Korea (South)
• PMID: 34984603 (Publication Type: Journal Article)
• Copyright: © 2022. The Pharmaceutical Society of Korea.

Chemical References

• Anti-Inflammatory Agents
• Cyclic Nucleotide Phosphodiesterases, Type 7
• Cytokines
• Dust
• Ovalbumin
• Sand
• 3-(N,N-dimethylsulfonamido)-4-methyl-nitrobenzene

Topics

• Animals
• Mice
• Anti-Inflammatory Agents (therapeutic use)
• Asthma (drug therapy, etiology)
• Bronchoalveolar Lavage Fluid (chemistry, cytology)
• Cyclic Nucleotide Phosphodiesterases, Type 7 (antagonists & inhibitors)
• Cytokines (analysis)
• Disease Models, Animal
• Dust
• Fluorescent Antibody Technique
• Inhalation Exposure (adverse effects)
• Lung (pathology)
• Mice, Inbred BALB C
• Ovalbumin (adverse effects)
• Pneumonia (chemically induced, drug therapy, pathology)
• Sand