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Updated: Aug 6, 2026
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Oropharyngeal Administration of Bleomycin in the Murine Model of Pulmonary Fibrosis
Published on: May 9, 2025
IL-17RA/IL-17RC Blockade Restores Fibrinolytic Balance in Bleomycin-induced Acute Lung Injury
Rakshitha Charavu1, Jeena Thrikkandiyoor Madambath1, Akarsha B Jain1,2
1Cell Biology & Molecular Genetics Division, Yenepoya Research Centre, Yenepoya Deemed to be University, Mangalore, Karnataka, India.
Recent Advances in Inflammation & Allergy Drug Discovery
|July 22, 2026
Summary
Targeting Interleukin-17 receptors (IL-17RA and IL-17RC) with neutralizing antibodies effectively reduces inflammation and restores normal fibrinolytic balance in acute lung injury (ALI). This approach shows promise for treating ALI and Acute Respiratory Distress Syndrome (ARDS).
Area of Science:
- Pulmonary Medicine
- Immunology
- Molecular Biology
Background:
- Interleukin-17A (IL-17A) signaling exacerbates inflammation and fibrotic remodeling in acute lung injury (ALI) by disrupting fibrinolysis.
- IL-17A signaling, mediated by IL-17RA and IL-17RC, triggers inflammatory responses, compromises epithelial integrity, and impairs lung barrier function.
Purpose of the Study:
- To evaluate the therapeutic potential of IL-17RA and IL-17RC neutralizing antibodies in a bleomycin (BLM)-induced ALI model.
- To investigate the impact of IL-17 receptor blockade on inflammation and the fibrinolytic system in ALI.
Main Methods:
- Acute lung injury (ALI) was induced using bleomycin (BLM) in A549 cells and C57BL/6 mice.
- Cells and mice were treated with neutralizing antibodies against IL-17RA and IL-17RC.
- Lung tissues and cell pellets were analyzed for the expression of fibrinolytic factors and inflammatory markers.
Main Results:
- Bleomycin-induced ALI significantly increased plasminogen activator inhibitor-1 (PAI-1) expression.
- Neutralization of IL-17RA or IL-17RC reduced PAI-1 levels by over 90% and restored urokinase plasminogen activator (uPA) and its receptor (uPAR) expression.
- Treatment suppressed pro-inflammatory cytokines, including TNF-α and IL-6, in the BLM-induced ALI model.
Conclusions:
- IL-17RA and IL-17RC play a critical role in ALI pathogenesis, particularly in regulating inflammation and fibrinolysis.
- Neutralizing IL-17RA or IL-17RC effectively mitigates lung injury by reducing inflammation and restoring fibrinolytic balance.
- Receptor-specific IL-17 blockade represents a potential therapeutic strategy for improving outcomes in ALI and ARDS.
