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The Antimicrobial Peptide Cathelicidin Exerts Immunomodulatory Effects via Scavenger Receptors
An active form of cathelicidin antimicrobial peptide, LL-37, has immunomodulatory and stimulatory effects, though the specific pathways are not clear. The purpose of this study was to identify the cellular pathways by which LL-37 amplifies the inflammation induced by damage-associated molecular patt...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9821026/ https://www.ncbi.nlm.nih.gov/pubmed/36614313 http://dx.doi.org/10.3390/ijms24010875 |
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author | Amagai, Ryo Takahashi, Toshiya Terui, Hitoshi Fujimura, Taku Yamasaki, Kenshi Aiba, Setsuya Asano, Yoshihide |
author_facet | Amagai, Ryo Takahashi, Toshiya Terui, Hitoshi Fujimura, Taku Yamasaki, Kenshi Aiba, Setsuya Asano, Yoshihide |
author_sort | Amagai, Ryo |
collection | PubMed |
description | An active form of cathelicidin antimicrobial peptide, LL-37, has immunomodulatory and stimulatory effects, though the specific pathways are not clear. The purpose of this study was to identify the cellular pathways by which LL-37 amplifies the inflammation induced by damage-associated molecular patterns (DAMPs). We performed DNA microarray, reverse transcription polymerase chain reaction, immunoblotting, and proximity ligation assays using cultured keratinocytes treated with LL-37 and/or the DAMP poly(I:C), a synthetic double-stranded RNA. In contrast to the combination of LL-37 and poly(I:C), LL-37 alone induced genes related to biological metabolic processes such as VEGFA and PTGS2 (COX-2). Inhibition of FPR2, a known receptor for cathelicidin, partially suppressed the induction of VEGFA and PTGS2. Importantly, VEGFA and PTGS2 induced by LL-37 alone were diminished by the knockdown of scavenger receptors including SCARB1 (SR-B1), OLR1 (SR-E1), and AGER (SR-J1). Moreover, LL-37 alone, as well as the combination of LL-37 and poly(I:C), showed proximity to the scavenger receptors, indicating that LL-37 acts via scavenger receptors and intermediates between them and poly(I:C). These results showed that the broad function of cathelicidin is generally dependent on scavenger receptors. Therefore, inhibitors of scavenger receptors or non-functional mock cathelicidin peptides may serve as new anti-inflammatory and immunosuppressive agents. |
format | Online Article Text |
id | pubmed-9821026 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-98210262023-01-07 The Antimicrobial Peptide Cathelicidin Exerts Immunomodulatory Effects via Scavenger Receptors Amagai, Ryo Takahashi, Toshiya Terui, Hitoshi Fujimura, Taku Yamasaki, Kenshi Aiba, Setsuya Asano, Yoshihide Int J Mol Sci Article An active form of cathelicidin antimicrobial peptide, LL-37, has immunomodulatory and stimulatory effects, though the specific pathways are not clear. The purpose of this study was to identify the cellular pathways by which LL-37 amplifies the inflammation induced by damage-associated molecular patterns (DAMPs). We performed DNA microarray, reverse transcription polymerase chain reaction, immunoblotting, and proximity ligation assays using cultured keratinocytes treated with LL-37 and/or the DAMP poly(I:C), a synthetic double-stranded RNA. In contrast to the combination of LL-37 and poly(I:C), LL-37 alone induced genes related to biological metabolic processes such as VEGFA and PTGS2 (COX-2). Inhibition of FPR2, a known receptor for cathelicidin, partially suppressed the induction of VEGFA and PTGS2. Importantly, VEGFA and PTGS2 induced by LL-37 alone were diminished by the knockdown of scavenger receptors including SCARB1 (SR-B1), OLR1 (SR-E1), and AGER (SR-J1). Moreover, LL-37 alone, as well as the combination of LL-37 and poly(I:C), showed proximity to the scavenger receptors, indicating that LL-37 acts via scavenger receptors and intermediates between them and poly(I:C). These results showed that the broad function of cathelicidin is generally dependent on scavenger receptors. Therefore, inhibitors of scavenger receptors or non-functional mock cathelicidin peptides may serve as new anti-inflammatory and immunosuppressive agents. MDPI 2023-01-03 /pmc/articles/PMC9821026/ /pubmed/36614313 http://dx.doi.org/10.3390/ijms24010875 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Amagai, Ryo Takahashi, Toshiya Terui, Hitoshi Fujimura, Taku Yamasaki, Kenshi Aiba, Setsuya Asano, Yoshihide The Antimicrobial Peptide Cathelicidin Exerts Immunomodulatory Effects via Scavenger Receptors |
title | The Antimicrobial Peptide Cathelicidin Exerts Immunomodulatory Effects via Scavenger Receptors |
title_full | The Antimicrobial Peptide Cathelicidin Exerts Immunomodulatory Effects via Scavenger Receptors |
title_fullStr | The Antimicrobial Peptide Cathelicidin Exerts Immunomodulatory Effects via Scavenger Receptors |
title_full_unstemmed | The Antimicrobial Peptide Cathelicidin Exerts Immunomodulatory Effects via Scavenger Receptors |
title_short | The Antimicrobial Peptide Cathelicidin Exerts Immunomodulatory Effects via Scavenger Receptors |
title_sort | antimicrobial peptide cathelicidin exerts immunomodulatory effects via scavenger receptors |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9821026/ https://www.ncbi.nlm.nih.gov/pubmed/36614313 http://dx.doi.org/10.3390/ijms24010875 |
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