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...
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MDPI AG
2023-01-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/1/875 |
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| author | Ryo Amagai Toshiya Takahashi Hitoshi Terui Taku Fujimura Kenshi Yamasaki Setsuya Aiba Yoshihide Asano |
| author_facet | Ryo Amagai Toshiya Takahashi Hitoshi Terui Taku Fujimura Kenshi Yamasaki Setsuya Aiba Yoshihide Asano |
| author_sort | Ryo Amagai |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-03-11T09:57:58Z |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-11T09:57:58Z |
| publishDate | 2023-01-01 |
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| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-8548af6475cf42f9a69952c861b62e412023-11-16T15:39:39ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-01-0124187510.3390/ijms24010875The Antimicrobial Peptide Cathelicidin Exerts Immunomodulatory Effects via Scavenger ReceptorsRyo Amagai0Toshiya Takahashi1Hitoshi Terui2Taku Fujimura3Kenshi Yamasaki4Setsuya Aiba5Yoshihide Asano6Department of Dermatology, Tohoku University Graduate School of Medicine, Sendai 980-8574, JapanDepartment of Dermatology, Tohoku University Graduate School of Medicine, Sendai 980-8574, JapanDepartment of Dermatology, Tohoku University Graduate School of Medicine, Sendai 980-8574, JapanDepartment of Dermatology, Tohoku University Graduate School of Medicine, Sendai 980-8574, JapanDepartment of Dermatology, Tohoku University Graduate School of Medicine, Sendai 980-8574, JapanDepartment of Dermatology, Tohoku University Graduate School of Medicine, Sendai 980-8574, JapanDepartment of Dermatology, Tohoku University Graduate School of Medicine, Sendai 980-8574, JapanAn 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.https://www.mdpi.com/1422-0067/24/1/875cathelicidinscavenger receptorsdamage-associated molecular patterns (DAMPs)psoriasisinnate immunity |
| spellingShingle | Ryo Amagai Toshiya Takahashi Hitoshi Terui Taku Fujimura Kenshi Yamasaki Setsuya Aiba Yoshihide Asano The Antimicrobial Peptide Cathelicidin Exerts Immunomodulatory Effects via Scavenger Receptors International Journal of Molecular Sciences cathelicidin scavenger receptors damage-associated molecular patterns (DAMPs) psoriasis innate immunity |
| 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 | cathelicidin scavenger receptors damage-associated molecular patterns (DAMPs) psoriasis innate immunity |
| url | https://www.mdpi.com/1422-0067/24/1/875 |
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