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Pirfenidone Alleviates Against Fine Particulate Matter-Induced Pulmonary Fibrosis Modulating via TGF-β1/TAK1/MKK3/p38
Jun-Seok Sung1, Il-Gyu Ko2, Lakkyong Hwang1,3
1Department of Physiology, College of Medicine, Kyung Hee University, Seoul 02447, Republic of Korea.
Abstract:
Increased exposure to particulate matter (PM) from air pollution causes lung inflammation and increases morbidity and mortality due to respiratory diseases. Pirfenidone is an anti-fibrotic agent used to treat idiopathic pulmonary fibrosis. Background/Objectives: In this experiment, we studied the therapeutic effects of pirfenidone on PM-induced pulmonary fibrosis. Methods: Pulmonary fibrosis was induced by the intratracheal application of 100 μg/kg PM10 mixed with 200 μL saline. After 42 days of PM10 infusion, 0.2 mL of distilled water with pirfenidone was orally administered to the pirfenidone-treated groups (200 and 400 mg/kg) every other day for a total of 15 times over 30 days. Results: The intratracheal administration of PM resulted in lung injury and a significant decrease in the number of bronchoalveolar lavage fluid cells. PM administration increased the lung injury score, level of lung fibrosis, and production of pro-inflammatory cytokines. Pirfenidone treatment effectively suppressed transforming growth factor-β-activated kinase 1 in PM-induced pulmonary fibrosis. The present changes inhibited the expressions of mitogen-activated protein kinase kinase 3 and p38, which suppressed transforming growth factor-β, ultimately alleviating lung fibrosis. PM exposure upregulated the expressions of fibronectin and type 1 collagen. PM exposure enhanced connective tissue growth factor and hydroxyproline levels in the lung tissue. The levels of these fibrosis-related factors were inhibited by pirfenidone treatment. Conclusions: These results suggest that pirfenidone is therapeutically effective against PM-induced pulmonary fibrosis.
Insights
Pirfenidone effectively treats particulate matter (PM)-induced lung fibrosis by reducing inflammation and fibrosis markers. This study shows pirfenidone
Area of Science:
- Environmental Health
- Pulmonary Medicine
- Pharmacology
Background:
- Particulate matter (PM) air pollution is a significant cause of lung inflammation, respiratory disease, and mortality.
- Idiopathic pulmonary fibrosis is treated with pirfenidone, an anti-fibrotic agent.
Purpose of the Study:
- To investigate the therapeutic potential of pirfenidone in mitigating pulmonary fibrosis induced by PM exposure.
- To elucidate the molecular mechanisms underlying pirfenidone's protective effects against PM-induced lung injury.
Main Methods:
- Pulmonary fibrosis was induced in rats via intratracheal instillation of PM10.
- Pirfenidone (200 and 400 mg/kg) was administered orally every other day for 30 days post-PM10 exposure.
- Lung injury, fibrosis scores, pro-inflammatory cytokines, and fibrosis-related markers were assessed.
Main Results:
- PM10 exposure led to significant lung injury, increased fibrosis, and elevated pro-inflammatory cytokines.
- Pirfenidone treatment suppressed key signaling pathways, including TGF-β-activated kinase 1, MAPK, and p38.
- Pirfenidone reduced the expression of fibrosis markers such as fibronectin, type 1 collagen, CTGF, and hydroxyproline.
Conclusions:
- Pirfenidone demonstrates significant therapeutic efficacy against PM-induced pulmonary fibrosis.
- The drug alleviates lung fibrosis by inhibiting inflammatory and fibrotic signaling pathways.
- Pirfenidone represents a potential therapeutic strategy for managing air pollution-related lung diseases.
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