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Original Article
- Blocking Toll-like receptor 9 attenuates bleomycin-induced pulmonary injury
- Badr Alzahrani, Mohamed M. S. Gaballa, Ahmed A. Tantawy, Maha A. Moussa, Salma A. Shoulah, Said M. Elshafae
- J Pathol Transl Med. 2022;56(2):81-91. Published online March 2, 2022
- DOI: https://doi.org/10.4132/jptm.2021.12.27
- 5,477 View
- 134 Download
- 9 Web of Science
- 8 Crossref
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Abstract
PDF - Background
Acute respiratory distress syndrome (ARDS) is one of the most common complications in coronavirus disease 2019 patients suffering from acute lung injury (ALI). In ARDS, marked distortion of pulmonary architecture has been reported. The pulmonary lesions in ARDS include hemodynamic derangements (such as alveolar edema and hemorrhage), vascular and bronchiolar damage, interstitial inflammatory cellular aggregations, and eventually fibrosis. Bleomycin induces ARDS-representative pulmonary damage in mice and rats; therefore, we used bleomycin model mice in our study. Recently, Toll-like receptor 9 (TLR9) was implicated in the development of ARDS and ALI.
Methods
In this study, we evaluated the efficiency of a TLR9 blocker (ODN2088) on bleomycin-induced pulmonary damage. We measured the apoptosis rate, inflammatory reaction, and fibroplasia in bleomycin- and bleomycin + ODN2088-treated mice.
Results
Our results showed a significant amelioration in bleomycin-induced damage to pulmonary architecture following ODN2088 treatment. A marked decrease in pulmonary epithelial and endothelial apoptosis rate as measured by cleaved caspase-3 expression, inflammatory reaction as indicated by tumor necrosis factor α expression, and pulmonary fibrosis as demonstrated by Van Gieson staining and α-smooth muscle actin immunohistochemistry were observed following ODN2088 treatment.
Conclusions
All these findings indicate that blocking downstream TLR9 signaling could be beneficial in prevention or mitigation of ARDS through hemodynamic derangements, inflammation, apoptosis, and fibrosis. -
Citations
Citations to this article as recorded by
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Clinical and Experimental Immunology.2025;[Epub] CrossRef - Toll-like Receptor 9 Inhibition Mitigates Fibroproliferative Responses in Translational Models of Pulmonary Fibrosis
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Scientific Reports.2024;[Epub] CrossRef - Suppression of miR-17 Alleviates Acute Respiratory Distress-associated Lung Fibrosis by Regulating Mfn2
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Current Medical Science.2024; 44(5): 964. CrossRef - TLR9: A friend or a foe
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Life Sciences.2022; 307: 120874. CrossRef
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