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MrgX2-mediated internalization of LL-37 and degranulation of human LAD2 mast cells

LL-37 is the sole antimicrobial peptide of human cathelicidin comprising 37 amino acids, which is expressed mainly in epithelial cells and neutrophils, and activates mast cells. In the present study, in order to elucidate the mechanism of mast cell activation by LL-37, the associations between the i...

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Autores principales: Murakami, Taisuke, Suzuki, Kaori, Niyonsaba, Francois, Tada, Hiroyuki, Reich, Johannes, Tamura, Hiroshi, Nagaoka, Isao
Formato: Online Artículo Texto
Lenguaje:English
Publicado: D.A. Spandidos 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6236315/
https://www.ncbi.nlm.nih.gov/pubmed/30280189
http://dx.doi.org/10.3892/mmr.2018.9532
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author Murakami, Taisuke
Suzuki, Kaori
Niyonsaba, Francois
Tada, Hiroyuki
Reich, Johannes
Tamura, Hiroshi
Nagaoka, Isao
author_facet Murakami, Taisuke
Suzuki, Kaori
Niyonsaba, Francois
Tada, Hiroyuki
Reich, Johannes
Tamura, Hiroshi
Nagaoka, Isao
author_sort Murakami, Taisuke
collection PubMed
description LL-37 is the sole antimicrobial peptide of human cathelicidin comprising 37 amino acids, which is expressed mainly in epithelial cells and neutrophils, and activates mast cells. In the present study, in order to elucidate the mechanism of mast cell activation by LL-37, the associations between the internalization of LL-37 and Mas-related gene X2 (MrgX2)-mediated mast cell activation (degranulation) was investigated using the human mast cell line, LAD2. LL-37 was rapidly internalized into the cells, and induced degranulation, as assessed by the extracellular release of β-hexosaminidase. Pertussis toxin, a G-protein inhibitor, significantly suppressed the internalization of LL-37 and the degranulation of LAD2 cells. Furthermore, small interfering (si)-RNA-mediated knockdown of MrgX2, a putative G protein-coupled receptor for LL-37, inhibited the internalization of LL-37 and degranulation of LAD2 cells. Notably, LL-37 internalization was enhanced by the stable expression of MrgX2 in HMC-1 and 293 cells. In addition, the internalized LL-37 mainly colocalized with MrgX2 in the perinuclear region of LAD2 cells. Furthermore, neuraminidase treatment, which removes negatively charged sialic acid from the cell surface, markedly reduced the internalization of LL-37 and degranulation of LAD2 cells, and clathrin-mediated endocytosis inhibitors (dynasore and chlorpromazine) inhibited the internalization and degranulation of LAD2 cells. Taken together, these observations indicated that LL-37 may bind the negatively charged cell surface molecules, rapidly internalize into the cells via clathrin-mediated endocytosis and interact with MrgX2 to activate mast cells (LAD2 cells).
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spelling pubmed-62363152018-11-19 MrgX2-mediated internalization of LL-37 and degranulation of human LAD2 mast cells Murakami, Taisuke Suzuki, Kaori Niyonsaba, Francois Tada, Hiroyuki Reich, Johannes Tamura, Hiroshi Nagaoka, Isao Mol Med Rep Articles LL-37 is the sole antimicrobial peptide of human cathelicidin comprising 37 amino acids, which is expressed mainly in epithelial cells and neutrophils, and activates mast cells. In the present study, in order to elucidate the mechanism of mast cell activation by LL-37, the associations between the internalization of LL-37 and Mas-related gene X2 (MrgX2)-mediated mast cell activation (degranulation) was investigated using the human mast cell line, LAD2. LL-37 was rapidly internalized into the cells, and induced degranulation, as assessed by the extracellular release of β-hexosaminidase. Pertussis toxin, a G-protein inhibitor, significantly suppressed the internalization of LL-37 and the degranulation of LAD2 cells. Furthermore, small interfering (si)-RNA-mediated knockdown of MrgX2, a putative G protein-coupled receptor for LL-37, inhibited the internalization of LL-37 and degranulation of LAD2 cells. Notably, LL-37 internalization was enhanced by the stable expression of MrgX2 in HMC-1 and 293 cells. In addition, the internalized LL-37 mainly colocalized with MrgX2 in the perinuclear region of LAD2 cells. Furthermore, neuraminidase treatment, which removes negatively charged sialic acid from the cell surface, markedly reduced the internalization of LL-37 and degranulation of LAD2 cells, and clathrin-mediated endocytosis inhibitors (dynasore and chlorpromazine) inhibited the internalization and degranulation of LAD2 cells. Taken together, these observations indicated that LL-37 may bind the negatively charged cell surface molecules, rapidly internalize into the cells via clathrin-mediated endocytosis and interact with MrgX2 to activate mast cells (LAD2 cells). D.A. Spandidos 2018-12 2018-10-02 /pmc/articles/PMC6236315/ /pubmed/30280189 http://dx.doi.org/10.3892/mmr.2018.9532 Text en Copyright: © Murakami et al. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
spellingShingle Articles
Murakami, Taisuke
Suzuki, Kaori
Niyonsaba, Francois
Tada, Hiroyuki
Reich, Johannes
Tamura, Hiroshi
Nagaoka, Isao
MrgX2-mediated internalization of LL-37 and degranulation of human LAD2 mast cells
title MrgX2-mediated internalization of LL-37 and degranulation of human LAD2 mast cells
title_full MrgX2-mediated internalization of LL-37 and degranulation of human LAD2 mast cells
title_fullStr MrgX2-mediated internalization of LL-37 and degranulation of human LAD2 mast cells
title_full_unstemmed MrgX2-mediated internalization of LL-37 and degranulation of human LAD2 mast cells
title_short MrgX2-mediated internalization of LL-37 and degranulation of human LAD2 mast cells
title_sort mrgx2-mediated internalization of ll-37 and degranulation of human lad2 mast cells
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6236315/
https://www.ncbi.nlm.nih.gov/pubmed/30280189
http://dx.doi.org/10.3892/mmr.2018.9532
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