Endoplasmic reticulum stress influences bronchial asthma pathogenesis by modulating nuclear factor κB activation

Area of Science:

• Immunology
• Cellular Biology
• Respiratory Medicine

Background:

• Endoplasmic reticulum (ER) stress is linked to inflammatory diseases, but its role in bronchial asthma remains understudied.
• Limited research exists on ER stress markers in asthmatic patients.

Purpose of the Study:

• To investigate the involvement of ER stress in the pathogenesis of bronchial asthma.
• To determine ER stress marker levels in asthmatic patients and animal models.

Main Methods:

• Utilized ovalbumin (OVA)-sensitized and lipopolysaccharide (LPS)-challenged mice (OVA(LPS)-OVA) and OVA-sensitized/challenged mice (OVA-OVA).
• Assessed ER stress markers in lung tissue, peripheral blood mononuclear cells (PBMCs), and bronchoalveolar lavage fluid (BALF) from mice and human asthmatic patients.
• Administered 4-phenylbutyric acid (4-PBA) to evaluate its therapeutic effects on ER stress and asthma features.

Main Results:

• OVA(LPS)-OVA mice exhibited significantly increased ER stress and unfolded protein response markers in lung tissue post-OVA challenge.
• Asthmatic patients showed dramatically elevated ER stress markers in PBMCs and BALF compared to healthy controls.
• 4-PBA treatment in mice reduced ER stress, nuclear factor κB (NF-κB) activation, inflammation, and airway hyperresponsiveness, while increasing IL-10 levels.

Conclusions:

• ER stress plays a role in bronchial asthma pathogenesis, potentially via modulation of NF-κB activation.
• 4-PBA demonstrates therapeutic potential by alleviating established asthmatic features.