The thrombin-derived host defense peptide GKY25 inhibits endotoxin-induced responses through Interactions with lipopolysaccharide and macrophages/monocytes
Host defense peptides have recently gained much interest as novel anti-infectives owing to their ability to kill bacteria and simultaneously modulate host cell responses. The cationic host defense peptide GKY25 (GKYGFYTHVFRLKKWIQKVIDQFGE), derived from the C terminus of human thrombin, inhibits proi...
| Main Authors: | , , , , , , |
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| Format: | Journal Article |
| Language: | English |
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2015
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| Online Access: | https://hdl.handle.net/10356/103339 http://hdl.handle.net/10220/25772 |
| _version_ | 1811678764152651776 |
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| author | Schmidtchen, Artur Morgelin, Matthias Hansen, Finja C. Kalle-Brune, Martina van der Plas, Mariena J. A. Strömdahl, Ann-Charlotte Malmsten, Martin |
| author2 | Lee Kong Chian School of Medicine (LKCMedicine) |
| author_facet | Lee Kong Chian School of Medicine (LKCMedicine) Schmidtchen, Artur Morgelin, Matthias Hansen, Finja C. Kalle-Brune, Martina van der Plas, Mariena J. A. Strömdahl, Ann-Charlotte Malmsten, Martin |
| author_sort | Schmidtchen, Artur |
| collection | NTU |
| description | Host defense peptides have recently gained much interest as novel anti-infectives owing to their ability to kill bacteria and simultaneously modulate host cell responses. The cationic host defense peptide GKY25 (GKYGFYTHVFRLKKWIQKVIDQFGE), derived from the C terminus of human thrombin, inhibits proinflammatory responses in vitro and in vivo, but the mode of action is unclear. In this study, we show that GKY25, apart from binding bacterial LPS, also interacts directly with monocytes and macrophages in vitro, ex vivo, and in vivo. Moreover, GKY25 inhibits TLR4- and TLR2-induced NF-κB activation in response to several microbe-derived agonists. Furthermore, GKY25 reduces LPS-induced phosphorylation of MAPKs p38α and JNK1/2/3. FACS and electron microscopy analyses showed that GKY25 interferes with TLR4/myeloid differentiation protein-2 dimerization. The results demonstrate a previously undisclosed activity of the host defense peptide GKY25, based on combined LPS and cell interactions leading to inhibition of TLR4 dimerization and subsequent reduction of NF-κB activity and proinflammatory cytokine production in monocytes and macrophages. |
| first_indexed | 2024-10-01T02:58:26Z |
| format | Journal Article |
| id | ntu-10356/103339 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2024-10-01T02:58:26Z |
| publishDate | 2015 |
| record_format | dspace |
| spelling | ntu-10356/1033392020-03-07T12:57:26Z The thrombin-derived host defense peptide GKY25 inhibits endotoxin-induced responses through Interactions with lipopolysaccharide and macrophages/monocytes Schmidtchen, Artur Morgelin, Matthias Hansen, Finja C. Kalle-Brune, Martina van der Plas, Mariena J. A. Strömdahl, Ann-Charlotte Malmsten, Martin Lee Kong Chian School of Medicine (LKCMedicine) DRNTU::Science::Biological sciences::Microbiology::Immunology Host defense peptides have recently gained much interest as novel anti-infectives owing to their ability to kill bacteria and simultaneously modulate host cell responses. The cationic host defense peptide GKY25 (GKYGFYTHVFRLKKWIQKVIDQFGE), derived from the C terminus of human thrombin, inhibits proinflammatory responses in vitro and in vivo, but the mode of action is unclear. In this study, we show that GKY25, apart from binding bacterial LPS, also interacts directly with monocytes and macrophages in vitro, ex vivo, and in vivo. Moreover, GKY25 inhibits TLR4- and TLR2-induced NF-κB activation in response to several microbe-derived agonists. Furthermore, GKY25 reduces LPS-induced phosphorylation of MAPKs p38α and JNK1/2/3. FACS and electron microscopy analyses showed that GKY25 interferes with TLR4/myeloid differentiation protein-2 dimerization. The results demonstrate a previously undisclosed activity of the host defense peptide GKY25, based on combined LPS and cell interactions leading to inhibition of TLR4 dimerization and subsequent reduction of NF-κB activity and proinflammatory cytokine production in monocytes and macrophages. 2015-06-05T02:05:09Z 2019-12-06T21:10:26Z 2015-06-05T02:05:09Z 2019-12-06T21:10:26Z 2015 2015 Journal Article Hansen, F. C., Kalle-Brune, M., van der Plas, M. J. A., Stromdahl, A. C., Malmsten, M., Morgelin, M., et al. (2015). The thrombin-derived host defense peptide GKY25 inhibits endotoxin-induced responses through Interactions with lipopolysaccharide and macrophages/monocytes. The journal of immunology, 194(11), 5397-5406. https://hdl.handle.net/10356/103339 http://hdl.handle.net/10220/25772 10.4049/jimmunol.1403009 en The journal of immunology © 2015 American Association of Immunologists (AAI). |
| spellingShingle | DRNTU::Science::Biological sciences::Microbiology::Immunology Schmidtchen, Artur Morgelin, Matthias Hansen, Finja C. Kalle-Brune, Martina van der Plas, Mariena J. A. Strömdahl, Ann-Charlotte Malmsten, Martin The thrombin-derived host defense peptide GKY25 inhibits endotoxin-induced responses through Interactions with lipopolysaccharide and macrophages/monocytes |
| title | The thrombin-derived host defense peptide GKY25 inhibits endotoxin-induced responses through Interactions with lipopolysaccharide and macrophages/monocytes |
| title_full | The thrombin-derived host defense peptide GKY25 inhibits endotoxin-induced responses through Interactions with lipopolysaccharide and macrophages/monocytes |
| title_fullStr | The thrombin-derived host defense peptide GKY25 inhibits endotoxin-induced responses through Interactions with lipopolysaccharide and macrophages/monocytes |
| title_full_unstemmed | The thrombin-derived host defense peptide GKY25 inhibits endotoxin-induced responses through Interactions with lipopolysaccharide and macrophages/monocytes |
| title_short | The thrombin-derived host defense peptide GKY25 inhibits endotoxin-induced responses through Interactions with lipopolysaccharide and macrophages/monocytes |
| title_sort | thrombin derived host defense peptide gky25 inhibits endotoxin induced responses through interactions with lipopolysaccharide and macrophages monocytes |
| topic | DRNTU::Science::Biological sciences::Microbiology::Immunology |
| url | https://hdl.handle.net/10356/103339 http://hdl.handle.net/10220/25772 |
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