Human cathelicidin antimicrobial peptide LL-37 promotes lymphangiogenesis in lymphatic endothelial cells through the ERK and Akt signaling pathways

LL-37, the only member of the cathelicidin family of cationic antimicrobial peptides in humans has been shown to exhibit a wide variety of biological actions in addition to its antimicrobial activity. However, the lymphangiogenic effect of LL-37 has not been elucidated yet. In this study, we examine...

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Bibliographic Details
Published in:Molecular biology reports 2020-09, Vol.47 (9), p.6841-6854
Main Authors: Yanagisawa, Takahiro, Ishii, Masakazu, Takahashi, Manami, Fujishima, Kei, Nishimura, Masahiro
Format: Article
Language:English
Subjects:
AKT protein
Animal Anatomy
Animal Biochemistry
Antimicrobial activity
Antimicrobial agents
Antimicrobial peptides
Biomedical and Life Sciences
Cationic antimicrobial peptides
Endothelial cells
Extracellular signal-regulated kinase
Formyl peptide receptor-like 1
Histology
Life Sciences
Microvasculature
Molecular modelling
Morphology
Original Article
Peptides
Phosphorylation
Signal transduction
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Summary:LL-37, the only member of the cathelicidin family of cationic antimicrobial peptides in humans has been shown to exhibit a wide variety of biological actions in addition to its antimicrobial activity. However, the lymphangiogenic effect of LL-37 has not been elucidated yet. In this study, we examined the effects of LL-37 on lymphangiogenesis and evaluated the underlying molecular mechanisms. LL-37 treatment significantly increased the migration and tube-like formation of human dermal lymphatic microvascular endothelial cells (HDLECs) and promoted the expression of lymphangiogenic factor in HDLECs. Treatment with LL-37 increased phosphorylation of ERK and Akt proteins in HDLECs, and pretreatment with ERK and Akt inhibitors significantly blocked the LL-37-induced HDLEC migration and tube-like formation. Furthermore, to investigate the involvement of formyl peptide receptor-like 1 (FPRL1) signaling in LL-37-induced lymphangiogenesis, HDLECs were treated with an FPRL1 antagonist. Pretreatment with the FPRL1 antagonist inhibited LL-37-induced phosphorylation of ERK and Akt proteins and attenuated LL-37-induced HDLEC migration and tube-like formation. These data indicated that LL-37 induces lymphangiogenesis in lymphatic endothelial cells via FPRL1, and the activation of the ERK and Akt-dependent signaling pathways.
ISSN:0301-4851
1573-4978
DOI:10.1007/s11033-020-05741-8