Azithromycin Attenuates Bleomycin-Induced Pulmonary Fibrosis Partly by Inhibiting the Expression of LOX and LOXL-2

Area of Science:

• Pulmonology
• Pharmacology
• Cell Biology

Background:

• Pulmonary fibrosis (PF) is a progressive lung disease characterized by tissue repair and remodeling.
• Azithromycin (AZM) exhibits anti-inflammatory and immune-regulatory properties, suggesting potential therapeutic benefits for PF.
• The precise mechanisms by which AZM may treat PF remain incompletely understood.

Purpose of the Study:

• To investigate the potential mechanisms of Azithromycin (AZM) in treating bleomycin (BLM)-induced pulmonary fibrosis (PF) in a mouse model.
• To explore AZM's effects on key fibrotic markers and signaling pathways in vitro and in vivo.

Main Methods:

• Established a mouse model of pulmonary fibrosis (PF) induced by bleomycin (BLM).
• Utilized primary mouse lung fibroblasts stimulated with transforming growth factor-beta1 (TGF-β1) for in vitro studies.
• Assessed the expression of alpha-smooth muscle actin (α-SMA), type I collagen, lysyl oxidase (LOX), and lysyl oxidase-like protein 2 (LOXL2).
• Investigated the involvement of TGF-β1/Smad and JNK/c-Jun signaling pathways.

Main Results:

• AZM treatment significantly reduced mortality, lung inflammation, and overall fibrosis in BLM-induced PF mice.
• AZM decreased the expression of α-SMA, type I collagen, LOX, and LOXL2 in lung tissues.
• In vitro, AZM inhibited type I collagen, LOX, LOXL2, and the JNK/c-Jun pathway in TGF-β1-stimulated fibroblasts, similar to a JNK-specific inhibitor.

Conclusions:

• Azithromycin (AZM) demonstrates a therapeutic effect in attenuating bleomycin-induced pulmonary fibrosis (PF) in mice.
• AZM's mechanism involves the partial inhibition of the JNK/c-Jun and TGF-β1/Smad signaling pathways.
• Reduced production of LOX and LOXL2 is a key factor in AZM's antifibrotic action.