LL-37 Exacerbates Local Inflammation in Sepsis-Induced Acute Lung Injury by Preventing Mitochondrial DNA (mtDNA) Degradation-Induced Autophagy
| العنوان: | LL-37 Exacerbates Local Inflammation in Sepsis-Induced Acute Lung Injury by Preventing Mitochondrial DNA (mtDNA) Degradation-Induced Autophagy |
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| المؤلفون: | Yiyu Yang, Zhiyuan Wu, Run Dang, Yunlong Zuo, Hongyan Peng |
| المصدر: | Medical Science Monitor : International Medical Journal of Experimental and Clinical Research |
| بيانات النشر: | International Scientific Literature, Inc., 2019. |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | Lipopolysaccharides, Male, Neutrophils, Acute Lung Injury, Inflammation, 030204 cardiovascular system & hematology, Lung injury, DNA, Mitochondrial, Proinflammatory cytokine, Sepsis, 03 medical and health sciences, Mice, 0302 clinical medicine, Downregulation and upregulation, Clinical Research, Cathelicidins, medicine, Autophagy, Animals, Humans, Lung, biology, business.industry, General Medicine, Lung Injury, Pneumonia, medicine.disease, Mitochondria, Disease Models, Animal, medicine.anatomical_structure, HEK293 Cells, 030220 oncology & carcinogenesis, Child, Preschool, Immunology, biology.protein, Cytokines, Female, medicine.symptom, Antibody, business, Antimicrobial Cationic Peptides |
| الوصف: | BACKGROUND Recent studies have proved that autophagy dysfunction in proinflammatory cells is involved in tissue damage and an excessive inflammatory response in sepsis. In the present study, we identified that the human antimicrobial peptide LL-37 facilitates resistance to DNase II-induced mitochondrial DNA (mtDNA) degradation and subsequent autophagy. MATERIAL AND METHODS We found higher serum levels of LL-37 in patients with severe sepsis compared to that in patients with mild sepsis. Neutrophils isolated from mice with sepsis after treatment with Cramp-mtDNA produced an excess of proinflammatory cytokines, including IL-1s, IL-6, IL-8, MMP-8, and TNF-alpha. Cramp-mtDNA in the lung samples from model animals with sepsis was detected by immunohistochemical staining. RESULTS Exogenous delivery of Cramp-mtDNA complex significantly exacerbated lung inflammation but the antibody against Cramp-mtDNA attenuated the excessive inflammatory response in LPS-induced acute lung injury. The expression of proinflammatory cytokines in lungs was upregulated and downregulated after treatment with the complex and antibody, respectively. LC-3 expression in 16HBE cells increased after LPS induction, irrespective of stimulation with LL-37. CONCLUSIONS These data show that LL-37 treatment worsens local inflammation in sepsis-induced acute lung injury by preventing mtDNA degradation-induced autophagy. |
| اللغة: | English |
| تدمد: | 1643-3750 1234-1010 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::6181ea85385d9b9b7b7d76452319aa55 http://europepmc.org/articles/PMC6711262 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....6181ea85385d9b9b7b7d76452319aa55 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 16433750 12341010 |
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