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Medical AI Inquiry: You was designed to assist in medical decision-making based on the provided user questions. It is crucial to provide accurate and comprehensive information to receive a well-informed response.  Labels: BACKGROUND, RESULTS. Meshes: Acute Lung Injury, Animals, Bleomycin, Bronchoalveolar Lavage Fluid, Cell Line, Cell Line, Tumor, Collagen Type I, DNA, Mitochondrial, Deoxyribonuclease I, Epithelial Cells, Humans, Interleukin-1beta, Interleukin-6, Male, Mice, Mice, Inbred C57BL, Mitochondria, Paraquat, Protective Agents, Pulmonary Fibrosis, Transforming Growth Factor beta1, Tumor Necrosis Factor-alpha.
user
Does dNaseI protect against Paraquat-induced acute lung injury and pulmonary fibrosis mediated by mitochondrial DNA? Context: Paraquat (PQ) poisoning is a lethal toxicological challenge that served as a disease model of acute lung injury and pulmonary fibrosis, but the mechanism is undetermined and no effective treatment has been discovered. We demonstrated that PQ injures mitochondria and leads to mtDNA release. The mtDNA mediated PBMC recruitment and stimulated the alveolar epithelial cell production of TGF-β1 in vitro. The levels of mtDNA in circulation and bronchial alveolar lavage fluid (BALF) were elevated in a mouse of PQ-induced lung injury. DNaseI could protect PQ-induced lung injury and significantly improved survival. Acute lung injury markers, such as TNFα, IL-1β, and IL-6, and marker of fibrosis, collagen I, were downregulated in parallel with the elimination of mtDNA by DNaseI. These data indicate a possible mechanism for PQ-induced, mtDNA-mediated lung injury, which may be shared by other causes of lung injury, as suggested by the same protective effect of DNaseI in bleomycin-induced lung injury model. Interestingly, increased mtDNA in the BALF of patients with amyopathic dermatomyositis-interstitial lung disease can be appreciated.
assistant
DNaseI targeting mtDNA may be a promising approach for the treatment of PQ-induced acute lung injury and pulmonary fibrosis that merits fast tracking through clinical trials. Final Decision: yes