Effects of frog skin peptide temporin-1CEa and its analogs on ox-LDL induced macrophage-derived foam cells

Purpose: Atherosclerosis is one of the most important pathological foundations of cardiovascular and cerebrovascular diseases with high morbidity and mortality. Studies have shown that macrophages play important roles in lipid accumulation in the vascular wall and thrombosis formation in atheroscler...

Full description

Bibliographic Details
Main Authors: Xue-Feng Yang, Xin Liu, Xiao-Yi Yan, De-Jing Shang
Format: Article
Language:English
Published: Frontiers Media S.A. 2023-03-01
Series:Frontiers in Pharmacology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fphar.2023.1139532/full
_version_ 1827986790841057280
author Xue-Feng Yang
Xue-Feng Yang
Xin Liu
Xiao-Yi Yan
De-Jing Shang
author_facet Xue-Feng Yang
Xue-Feng Yang
Xin Liu
Xiao-Yi Yan
De-Jing Shang
author_sort Xue-Feng Yang
collection DOAJ
description Purpose: Atherosclerosis is one of the most important pathological foundations of cardiovascular and cerebrovascular diseases with high morbidity and mortality. Studies have shown that macrophages play important roles in lipid accumulation in the vascular wall and thrombosis formation in atherosclerotic plaques. This study aimed to explore the effect of frog skin antimicrobial peptides (AMPs) temporin-1CEa and its analogs on ox-LDL induced macrophage-derived foam cells.Methods: CCK-8, ORO staining, and intracellular cholesterol measurements were used to study cellular activity, lipid droplet formation and cholesterol levels, respectively. ELISA, real-time quantitative PCR, Western blotting and flow cytometry analysis were used to study the expression of inflammatory factors, mRNA and proteins associated with ox-LDL uptake and cholesterol efflux in macrophage-derived foam cells, respectively. Furthermore, the effects of AMPs on inflammation signaling pathways were studied.Results: Frog skin AMPs could significantly increase the cell viability of the ox-LDL-induced foaming macrophages and decrease the formation of intracellular lipid droplets and the levels of total cholesterol and cholesterol ester (CE). Frog skin AMPs inhibited foaming formation by reducing the protein expression of CD36, which regulates ox-LDL uptake but had no effect on the expression of efflux proteins ATP binding cassette subfamily A/G member 1 (ABCA1/ABCG1). Then, decreased mRNA expression of NF-κB and protein expression of p-NF-κB p65, p-IκB, p-JNK, p-ERK, p-p38 and the release of TNF-α and IL-6 occurred after exposure to the three frog skin AMPs.Conclusion: Frog skin peptide temporin-1CEa and its analogs can improve the ox-LDL induced formation of macrophage-derived foam cells, in addition, inhibit inflammatory cytokine release through inhibiting the NF-κB and MAPK signaling pathways, thereby inhibiting inflammatory responses in atherosclerosis.
first_indexed 2024-04-09T23:36:58Z
format Article
id doaj.art-1bf315fe140b4752bda146ef39fa7353
institution Directory Open Access Journal
issn 1663-9812
language English
last_indexed 2024-04-09T23:36:58Z
publishDate 2023-03-01
publisher Frontiers Media S.A.
record_format Article
series Frontiers in Pharmacology
spelling doaj.art-1bf315fe140b4752bda146ef39fa73532023-03-20T05:24:13ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122023-03-011410.3389/fphar.2023.11395321139532Effects of frog skin peptide temporin-1CEa and its analogs on ox-LDL induced macrophage-derived foam cellsXue-Feng Yang0Xue-Feng Yang1Xin Liu2Xiao-Yi Yan3De-Jing Shang4School of Life Science, Liaoning Provincial Key Laboratory of Biotechnology and Drug Discovery, Liaoning Normal University, Dalian, ChinaSchool of Basic Medical Sciences, Department of Physiology, Jinzhou Medical University, Jinzhou, ChinaSchool of Life Science, Liaoning Provincial Key Laboratory of Biotechnology and Drug Discovery, Liaoning Normal University, Dalian, ChinaSchool of Life Science, Liaoning Provincial Key Laboratory of Biotechnology and Drug Discovery, Liaoning Normal University, Dalian, ChinaSchool of Life Science, Liaoning Provincial Key Laboratory of Biotechnology and Drug Discovery, Liaoning Normal University, Dalian, ChinaPurpose: Atherosclerosis is one of the most important pathological foundations of cardiovascular and cerebrovascular diseases with high morbidity and mortality. Studies have shown that macrophages play important roles in lipid accumulation in the vascular wall and thrombosis formation in atherosclerotic plaques. This study aimed to explore the effect of frog skin antimicrobial peptides (AMPs) temporin-1CEa and its analogs on ox-LDL induced macrophage-derived foam cells.Methods: CCK-8, ORO staining, and intracellular cholesterol measurements were used to study cellular activity, lipid droplet formation and cholesterol levels, respectively. ELISA, real-time quantitative PCR, Western blotting and flow cytometry analysis were used to study the expression of inflammatory factors, mRNA and proteins associated with ox-LDL uptake and cholesterol efflux in macrophage-derived foam cells, respectively. Furthermore, the effects of AMPs on inflammation signaling pathways were studied.Results: Frog skin AMPs could significantly increase the cell viability of the ox-LDL-induced foaming macrophages and decrease the formation of intracellular lipid droplets and the levels of total cholesterol and cholesterol ester (CE). Frog skin AMPs inhibited foaming formation by reducing the protein expression of CD36, which regulates ox-LDL uptake but had no effect on the expression of efflux proteins ATP binding cassette subfamily A/G member 1 (ABCA1/ABCG1). Then, decreased mRNA expression of NF-κB and protein expression of p-NF-κB p65, p-IκB, p-JNK, p-ERK, p-p38 and the release of TNF-α and IL-6 occurred after exposure to the three frog skin AMPs.Conclusion: Frog skin peptide temporin-1CEa and its analogs can improve the ox-LDL induced formation of macrophage-derived foam cells, in addition, inhibit inflammatory cytokine release through inhibiting the NF-κB and MAPK signaling pathways, thereby inhibiting inflammatory responses in atherosclerosis.https://www.frontiersin.org/articles/10.3389/fphar.2023.1139532/fullfrog skin peptidefoam cellsatherosclerosislipid metabolisminflammation
spellingShingle Xue-Feng Yang
Xue-Feng Yang
Xin Liu
Xiao-Yi Yan
De-Jing Shang
Effects of frog skin peptide temporin-1CEa and its analogs on ox-LDL induced macrophage-derived foam cells
Frontiers in Pharmacology
frog skin peptide
foam cells
atherosclerosis
lipid metabolism
inflammation
title Effects of frog skin peptide temporin-1CEa and its analogs on ox-LDL induced macrophage-derived foam cells
title_full Effects of frog skin peptide temporin-1CEa and its analogs on ox-LDL induced macrophage-derived foam cells
title_fullStr Effects of frog skin peptide temporin-1CEa and its analogs on ox-LDL induced macrophage-derived foam cells
title_full_unstemmed Effects of frog skin peptide temporin-1CEa and its analogs on ox-LDL induced macrophage-derived foam cells
title_short Effects of frog skin peptide temporin-1CEa and its analogs on ox-LDL induced macrophage-derived foam cells
title_sort effects of frog skin peptide temporin 1cea and its analogs on ox ldl induced macrophage derived foam cells
topic frog skin peptide
foam cells
atherosclerosis
lipid metabolism
inflammation
url https://www.frontiersin.org/articles/10.3389/fphar.2023.1139532/full
work_keys_str_mv AT xuefengyang effectsoffrogskinpeptidetemporin1ceaanditsanalogsonoxldlinducedmacrophagederivedfoamcells
AT xuefengyang effectsoffrogskinpeptidetemporin1ceaanditsanalogsonoxldlinducedmacrophagederivedfoamcells
AT xinliu effectsoffrogskinpeptidetemporin1ceaanditsanalogsonoxldlinducedmacrophagederivedfoamcells
AT xiaoyiyan effectsoffrogskinpeptidetemporin1ceaanditsanalogsonoxldlinducedmacrophagederivedfoamcells
AT dejingshang effectsoffrogskinpeptidetemporin1ceaanditsanalogsonoxldlinducedmacrophagederivedfoamcells