miR-155 Modulates Cockroach Allergen- and Oxidative Stress-Induced Cyclooxygenase-2 in Asthma

Area of Science:

• Immunology
• Molecular Biology
• Respiratory Medicine

Background:

• Cockroach allergen exposure is a significant asthma risk factor.
• Asthma involves airway epithelial damage and oxidative stress.
• Mechanisms of cockroach-induced oxidative stress in asthma require elucidation.

Purpose of the Study:

• To investigate cockroach allergen-induced oxidative stress in airway epithelium.
• To identify the underlying molecular mechanisms, focusing on gene and microRNA regulation.
• To explore the role of miR-155 and cyclooxygenase-2 (COX-2) in this process.

Main Methods:

• Human bronchial epithelial cells and miR-155 knockout mice were used.
• Cockroach extract (CRE) was applied to induce cellular responses.
• RT-PCR arrays, reporter assays, and biochemical analyses were performed.

Main Results:

• CRE induced reactive oxygen species (ROS) production, particularly mitochondrial ROS.
• Cyclooxygenase-2 (COX-2) was significantly upregulated by CRE.
• miR-155 was found to regulate COX-2 expression and stability, influencing ROS production.
• miR-155 knockout mice showed reduced ROS, COX-2, inflammation, and Th2/Th17 cytokines.
• Elevated plasma miR-155 levels were observed in severe asthmatics, especially those with cockroach allergy.

Conclusions:

• Cockroach allergen exposure induces oxidative stress in airway epithelium through the ROS-COX-2 pathway.
• miR-155 plays a critical role in regulating this pathway.
• Plasma miR-155 levels may serve as a biomarker for severe asthma and cockroach allergy.
• Targeting the miR-155/COX-2 axis presents a potential therapeutic strategy for asthma.