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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
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- 4 Web of Science
- 4 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
- Mechanisms underlying dose-limiting toxicities of conventional chemotherapeutic agents
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Journal of Chemotherapy.2024; : 1. CrossRef - Innate Immune Response-Mediated Inflammation in Viral Pneumonia
Weiwei Ni, Xin Wei, Rui Wu
Journal of Pediatric Infectious Diseases.2024;[Epub] CrossRef - Combination of losartan with pirfenidone: a protective anti-fibrotic against pulmonary fibrosis induced by bleomycin in rats
Arian Amirkhosravi, Maryamossadat Mirtajaddini Goki, Mahmoud Reza Heidari, Somayyeh Karami-Mohajeri, Maryam Iranpour, Maryam Torshabi, Mitra Mehrabani, Ali Mandegary, Mehrnaz Mehrabani
Scientific Reports.2024;[Epub] CrossRef - TLR9: A friend or a foe
Mona M. Saber, Nada Monir, Azza S. Awad, Marwa E. Elsherbiny, Hala F. Zaki
Life Sciences.2022; 307: 120874. CrossRef
- Mechanisms underlying dose-limiting toxicities of conventional chemotherapeutic agents
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