18 August 2019 : Clinical Research
LL-37 Exacerbates Local Inflammation in Sepsis-Induced Acute Lung Injury by Preventing Mitochondrial DNA (mtDNA) Degradation-Induced Autophagy
Yunlong Zuo1ABCDEFG, Run Dang1BC, Hongyan Peng1ABCF, Zhiyuan Wu1BC, Yiyu Yang1AE*DOI: 10.12659/MSM.915298
Med Sci Monit 2019; 25:6193-9203
Abstract
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-1β, IL-6, IL-8, MMP-8, and TNF-α. 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.
Keywords: Lung Injury, Sepsis, acute lung injury, Antimicrobial Cationic Peptides, Child, Preschool, Cytokines, DNA, Mitochondrial, HEK293 Cells, Lipopolysaccharides, Mitochondria, Neutrophils
Editorial
01 November 2024 : Editorial
Editorial: Artificial Intelligence (AI), Digital Image Analysis, and the Future of Cancer Diagnosis and PrognosisDOI: 10.12659/MSM.947038
Med Sci Monit 2024; 30:e947038
In Press
Clinical Research
Plaque Removal and Gingival Bleeding Using Biodegradable Toothbrushes: Salvadora persica, Bamboo, and Nylo...Med Sci Monit In Press; DOI: 10.12659/MSM.944469
Clinical Research
Comparative Analysis of Extended Curettage with Plate Fixation and Extended Curettage with Intramedullary N...Med Sci Monit In Press; DOI: 10.12659/MSM.945157
Clinical Research
Clinical Outcomes of Talus Bone Marrow Edema: Comparing Plaster Cast, Crutches, and Walking Boot TreatmentsMed Sci Monit In Press; DOI: 10.12659/MSM.946072
Review article
Comprehensive Insights into Arecoline Hydrobromide: Pharmacology, Toxicity, and PharmacokineticsMed Sci Monit In Press; DOI: 10.12659/MSM.945582
Most Viewed Current Articles
17 Jan 2024 : Review article 6,263,065
Vaccination Guidelines for Pregnant Women: Addressing COVID-19 and the Omicron VariantDOI :10.12659/MSM.942799
Med Sci Monit 2024; 30:e942799
14 Dec 2022 : Clinical Research 1,908,785
Prevalence and Variability of Allergen-Specific Immunoglobulin E in Patients with Elevated Tryptase LevelsDOI :10.12659/MSM.937990
Med Sci Monit 2022; 28:e937990
16 May 2023 : Clinical Research 695,294
Electrophysiological Testing for an Auditory Processing Disorder and Reading Performance in 54 School Stude...DOI :10.12659/MSM.940387
Med Sci Monit 2023; 29:e940387
07 Jan 2022 : Meta-Analysis 260,437
Efficacy and Safety of Light Therapy as a Home Treatment for Motor and Non-Motor Symptoms of Parkinson Dise...DOI :10.12659/MSM.935074
Med Sci Monit 2022; 28:e935074