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Methotrexate Induces Apoptosis in Organ-Cultured Nasal Polyps Via the Fas Pathway
Kyung Wook Heo1, Seong Kook Park, Yeo Myeong Lee
1*Department of Otorhinolaryngology-Head and Neck Surgery †Department of Anatomy and Research Center for Tumor Immunology, Inje University Busan Paik Hospital, Busan, South Korea.
Objective:
Methotrexate (MTX) is very effective when used to treat chronic inflammatory diseases, and also induces apoptosis in nasal polyps (NPs). Increasing evidence suggests that Fas-Fas ligand (FasL) interactions activate multiple pathways involved in the regulation of immune and inflammatory cell functions. The aim of the present study was to identify pathways activated by Fas signaling when NPs were treated with MTX.
Methods:
Nasal polyps tissues were cultured using an air-liquid interface organ culture method. Cultures were maintained in the absence or presence of MTX (10 or 100 μM) for 24 hours. The authors used the reverse transcription-polymerase chain reaction method and Western blotting to identify pathways activated by Fas when NPs were treated with MTX.
Results:
The Fas mRNA expression ratio was unchanged upon MTX treatment, but the FasL mRNA expression ratio was significantly higher in MTX-treated than nontreated polyps. In addition, the expression levels of the Fas and FasL proteins were significantly higher in polyps treated with both 10 and 100 μM MTX compared with nontreated polyps.
Conclusions:
Methotrexate induces apoptosis in NPs via the Fas pathway. Future studies should explore the topical use of MTX for NP control. Methotrexate may be a useful alternative steroid-sparing agent for the treatment of NPs.
Insights
Methotrexate (MTX) treatment increases Fas ligand (FasL) expression in nasal polyps (NPs), inducing apoptosis via the Fas pathway. This suggests MTX may be a steroid-sparing agent for NP treatment.
Area of Science:
- Immunology
- Cell Biology
- Pharmacology
Background:
- Methotrexate (MTX) is effective for chronic inflammatory diseases and induces apoptosis in nasal polyps (NPs).
- Fas-Fas ligand (FasL) interactions regulate immune and inflammatory cell functions.
- Understanding MTX's mechanism in NPs is crucial for treatment optimization.
Purpose of the Study:
- To identify pathways activated by Fas signaling in MTX-treated nasal polyps.
- To investigate the role of the Fas pathway in MTX-induced apoptosis in NPs.
- To explore MTX as a potential therapeutic agent for nasal polyps.
Main Methods:
- Nasal polyp tissues were cultured using an air-liquid interface organ culture method.
- Cultures were treated with MTX (10 or 100 μM) for 24 hours.
- Reverse transcription-polymerase chain reaction and Western blotting were used to analyze gene and protein expression.
Main Results:
- Fas mRNA expression remained unchanged, but FasL mRNA expression significantly increased in MTX-treated NPs.
- Both Fas and FasL protein levels were significantly elevated in polyps treated with MTX compared to controls.
- These findings indicate MTX upregulates the Fas pathway in nasal polyps.
Conclusions:
- Methotrexate induces apoptosis in nasal polyps through the Fas pathway.
- Topical application of MTX warrants further investigation for nasal polyp control.
- MTX presents a potential steroid-sparing alternative for treating nasal polyps.
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