LL‐37 and its analog FF/CAP18 attenuate neutrophil migration in sepsis‐induced acute lung injury

• Published in: Journal of cellular biochemistry 2019-04, Vol.120 (4), p.4863-4871
• Main Authors: Qin, Xiuchuan, Zhu, Guangfa, Huang, Lixue, Zhang, Wenwei, Huang, Yan, Xi, Xin
• Format: Article
• Language: English
• Subjects: acute lung injury; Acute Lung Injury - metabolism; Acute Lung Injury - pathology; Alanine; Alanine transaminase; Animals; Antimicrobial Cationic Peptides - pharmacology; Aspartate aminotransferase; Attenuation; Biocompatibility; Biomarkers - metabolism; Biomedical materials; Cecum; Cell Movement; Cytokines; Extracellular signal-regulated kinase; Focal adhesion kinase; Infiltration; Inflammation; Injuries; L-Lactate dehydrogenase; Lactate dehydrogenase; Lactic acid; Leukocyte migration; Leukocytes (neutrophilic); LL‐37; Lungs; MAP Kinase Signaling System - drug effects; Markers; Mice; neutrophil infiltration; Neutrophils; Neutrophils - metabolism; Neutrophils - pathology; Osteopontin; Peptides; Peroxidase; Proteins; Sepsis; Sepsis - metabolism; Sepsis - pathology
• ISSN: 0730-2312; 1097-4644
• DOI: 10.1002/jcb.27641

Introduction: Sepsis can result in acute lung injury. LL‐37 is a small cationic host defense peptide involved in anti‐inflammatory. In the current study, it was hypothesized that antimicrobial peptide LL‐37 could play a protective role in attenuating the progression of sepsis‐induced acute lung injury. Methods: Forty male C57BL/6 mice were induced into sepsis using cecal ligation and puncture, and subsequently administered with recombinant mouse osteopontin. Peptides LL‐37, the LL‐37 analog (FF/CAP18, called sLL‐37), or normal saline was intravenously administered into septic mice for 20 hours. Then, proinflammatory cytokines (IL‐6 and IL‐1β), acute lung injury markers (alanine aminotransferase [ALT], aspartate aminotransferase [AST], and lactate dehydrogenase [LDH]), the neutrophil infiltration marker (myeloperoxidase [MPO]), and neutrophil infiltration were detected. Furthermore, the neutrophil migration and expression of migration‐related factors (focal adhesion kinase [FAK], ERK, and P38) in differentiated HL‐60 cells were detected. Results: Septic mice had upregulated IL‐6, IL‐1β, ALT, AST, LDH, MPO, p‐FAK, p‐ERK, and p‐P38, infiltrated neutrophils, and migrated neutrophil‐like HL‐60 cells. In contrast, the administration of peptide LL‐37 and sLL‐37 inhibited all these changes. Compared with septic mice, it was found that proinflammatory cytokines, lung injury markers, MPO, and infiltrated neutrophils decreased in mice treated with LL‐37 and sLL‐37. In addition, the migrated neutrophil‐like HL‐60 cells and activated p‐FAK, p‐ERK, and p‐P38 proteins were suppressed by LL‐37 and sLL‐37 treatments. Conclusions: Peptide LL‐37 and its analog sLL‐37 attenuated the progression of sepsis‐induced acute lung injury by inhibiting neutrophil infiltration and migration through the FAK, ERK, and P38 pathways.