Profiling gene expression reveals insights into pulmonary response to aerosolized botulinum toxin type A exposure in mice

Abstract

Botulinum neurotoxin type A (BoNT/A) is traditional medicine and well known for its therapeutic use as an anesthetic and in cosmetic applications that work through the inhibition of acetylcholine exocytosis in neuronal cells. BoNT/A also has the potential to function as a biological weapon due to its high mortality rate and ease of dispersal. Emerging evidence suggests that BoNT/A exhibits biological effects on nonneuronal cells. In cytology experiments, BoNT/A induces global gene expression alterations. However, pulmonary effects from exposure to aerosolized BoNT/A have not been evaluated. This study investigated the global transcriptional profile of lung tissues after botulism inhalation. A mice model of inhaled botulism was established using intratracheal exposure to aerosolized BoNT/A and described through histological examination and flow cytometry. Transcriptomic analysis revealed that genes related to acute inflammatory responses were upregulated at 12‐h postexposure. Increased expression of multiple anti‐inflammatory marker genes and decreased expression of pro‐inflammatory marker genes were observed at 48‐ to 72‐h postexposure, underscoring a transcriptional shift toward a pro‐reparative phenotype. Histological examination and cell proportions analysis mirrored these expression patterns. Accordingly, the orchestration of a quick phenotype transition prompted by BoNT/A may have the potential for promoting the resolution of the inflammatory lung. To our knowledge, this study represents the first research to investigate the pulmonary transcriptional responses of aerosolized BoNT/A exposure; the results may provide new insights in elucidating the molecular mechanism for pulmonary inhaled botulism and highlight the potential therapeutic application of BoNT/A in mitigating inflammatory conditions.

Anti-Inflammatory Effects of BoNT/A Against Complete Freund’s Adjuvant-Induced Arthritis Pain in Rats: Transcriptome Analysis

“…Su et al systematically characterized the transcriptional responses of lung tissues for 72 h after aerosolized BoNT/A exposure; they found that the DEGs set IL-17, TNF-α, and NK-κB signaling pathways after 12 and 24 h of BoNT/A exposure, but there was an opposite change after 48 and 72 h of BoNT/A exposure, and the DEGs were enriched for antiinflammation functions, such as regulation of inflammatory response. Therefore, they suggest that the changes in expression profiles in these experimental groups indicate a shift from a pro-to an anti-inflammatory phenotype in the distal lung parenchyma, and that BoNT/A might show an anti-inflammatory effect in this change (Su et al, 2021). Olex et al found that another important signaling and metabolic pathway in the progression of osteoarthritis (OA) is the ECM-receptor interaction pathway (Olex et al, 2014).…”