Blocking Toll-like receptor 9 attenuates bleomycin-induced pulmonary injury

• Published in: Journal of pathology and translational medicine Vol. 56; no. 2; pp. 81 - 91
• Main Authors: Alzahrani, Badr, Gaballa, Mohamed M S, Tantawy, Ahmed A, Moussa, Maha A, Shoulah, Salma A, Elshafae, Said M
• Format: Journal Article
• Language: English
• Published: Korea (South) Korean Society of Pathologists, Korean Society for Cytopathology 01.03.2022; The Korean Society of Pathologists and the Korean Society for Cytopathology; Korean Society of Pathologists & the Korean Society for Cytopathology; 대한병리학회
• Subjects: acute respiratory distress syndrome; Albinism; Apoptosis; bleomycin; Collagen; Coronaviruses; COVID-19; Cytokines; Disease; Edema; fibrosis; Hemodynamics; Immune system; Inflammation; Laboratory animals; Ligands; odn2088; Original; Respiratory distress syndrome; Severe acute respiratory syndrome; Severe acute respiratory syndrome coronavirus 2; Smooth muscle; tlr9; Tumor necrosis factor-TNF; 병리학; United States > US; Egypt; Acute respiratory distress syndrome; TLR9; Bleomycin; Fibrosis; ODN2088
• ISSN: 2383-7837; 2383-7845
• DOI: 10.4132/jptm.2021.12.27

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. 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. 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. 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.