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eISSN: 1643-3750

Published: 2019-08-18

LL-37 Exacerbates Local Inflammation in Sepsis-Induced Acute Lung Injury by Preventing Mitochondrial DNA (mtDNA) Degradation-Induced Autophagy

Yunlong Zuo, Run Dang, Hongyan Peng, Zhiyuan Wu, Yiyu Yang

(Pediatric Intensive Care Unit, Guangzhou Women’s and Children’s Medical Center, Guangzhou, Guangdong, China (mainland))

Med Sci Monit 2019; 25:6193-9203

DOI: 10.12659/MSM.915298

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-1ß, 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.

Keywords: Autophagy, Lung Injury, Sepsis

Published: 2019-08-17

Role of CircRNAs_100395 in Proliferation and Metastases of Liver Cancer

Qiaming Chen, Zhian Chen, Sai Cao, Botang Guo, Yilin Chen, Zixin Feng, Jiaqi Wang, Guohu Guo, Xinhua Chen, Xianying Huang

Med Sci Monit 2019; 25:6181-6192

DOI: 10.12659/MSM.915963

Published: 2019-08-17

The Potential Effects of Diabetes Mellitus on Liver Fibrosis in Patients with Primary Biliary Cholangitis

Xu Liu, Hongqin Xu, Mengru Zhan, Junqi Niu

Med Sci Monit 2019; 25:6174-6180

DOI: 10.12659/MSM.916107