Immunomodulatory Functions of the Human Cathelicidin LL-37 (aa 13–31)-Derived Peptides are Associated with Predicted α-Helical Propensity and Hydrophobic Index
The anti-endotoxin activity of the cationic peptide LL-37 and its derivative IG-19 is attributed to electrostatic interaction of the peptides’ positive charge with negatively charged bacterial lipopolysaccharides (LPS), and in part to the alteration of intracellular mechanisms independent...
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| Format: | Article |
| Language: | English |
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MDPI AG
2019-09-01
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| Series: | Biomolecules |
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| Online Access: | https://www.mdpi.com/2218-273X/9/9/501 |
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| author | Mahadevappa Hemshekhar Sana Faiyaz Ka-Yee Grace Choi Oleg V. Krokhin Neeloffer Mookherjee |
| author_facet | Mahadevappa Hemshekhar Sana Faiyaz Ka-Yee Grace Choi Oleg V. Krokhin Neeloffer Mookherjee |
| author_sort | Mahadevappa Hemshekhar |
| collection | DOAJ |
| description | The anti-endotoxin activity of the cationic peptide LL-37 and its derivative IG-19 is attributed to electrostatic interaction of the peptides’ positive charge with negatively charged bacterial lipopolysaccharides (LPS), and in part to the alteration of intracellular mechanisms independent of peptide binding to LPS. We examined the immunomodulatory responses induced by IG-19 and four IG-19-derived scrambled peptides (IG-19a−d), in the presence and absence of LPS, in macrophages and peripheral blood-derived mononuclear cells. All peptides had identical net charge (+5) and amino acid composition, but different hydrophobicity and α-helical propensity. Peptide IG-19 suppressed LPS-induced cytokine/chemokine production by >90%, IG-19a and IG-19b suppressed it by 40−50%, and IG-19c and IG-19d did not suppress cytokine/chemokine production at all. In silico prediction algorithms and the peptide retention time (RT) on a C18 RP HPLC column indicated a linear association between α-helical propensity and hydrophobicity with the ability of the peptides to inhibit LPS-induced responses. Peptide RT exhibited a significant correlation (>70%) between the suppression of LPS-induced cytokine/chemokine production and peptide-induced production of the anti-inflammatory cytokine IL-1RA. These results indicate that RT on a C18 column can be used as a predictor for the immunomodulatory functions of cationic peptides. Overall, we demonstrated that the immunomodulatory functions of LL-37-derived peptides with identical positive charge and amino acid composition are directly associated with the predicted α-helical propensity and hydrophobicity of the peptides. |
| first_indexed | 2024-12-14T15:35:06Z |
| format | Article |
| id | doaj.art-f695932aa530465b979fb77252795f32 |
| institution | Directory Open Access Journal |
| issn | 2218-273X |
| language | English |
| last_indexed | 2024-12-14T15:35:06Z |
| publishDate | 2019-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomolecules |
| spelling | doaj.art-f695932aa530465b979fb77252795f322022-12-21T22:55:45ZengMDPI AGBiomolecules2218-273X2019-09-019950110.3390/biom9090501biom9090501Immunomodulatory Functions of the Human Cathelicidin LL-37 (aa 13–31)-Derived Peptides are Associated with Predicted α-Helical Propensity and Hydrophobic IndexMahadevappa Hemshekhar0Sana Faiyaz1Ka-Yee Grace Choi2Oleg V. Krokhin3Neeloffer Mookherjee4Manitoba Centre for Proteomics and Systems Biology, Department of Internal Medicine, University of Manitoba, Winnipeg, MB R3E3P4, CanadaManitoba Centre for Proteomics and Systems Biology, Department of Internal Medicine, University of Manitoba, Winnipeg, MB R3E3P4, CanadaManitoba Centre for Proteomics and Systems Biology, Department of Internal Medicine, University of Manitoba, Winnipeg, MB R3E3P4, CanadaManitoba Centre for Proteomics and Systems Biology, Department of Internal Medicine, University of Manitoba, Winnipeg, MB R3E3P4, CanadaManitoba Centre for Proteomics and Systems Biology, Department of Internal Medicine, University of Manitoba, Winnipeg, MB R3E3P4, CanadaThe anti-endotoxin activity of the cationic peptide LL-37 and its derivative IG-19 is attributed to electrostatic interaction of the peptides’ positive charge with negatively charged bacterial lipopolysaccharides (LPS), and in part to the alteration of intracellular mechanisms independent of peptide binding to LPS. We examined the immunomodulatory responses induced by IG-19 and four IG-19-derived scrambled peptides (IG-19a−d), in the presence and absence of LPS, in macrophages and peripheral blood-derived mononuclear cells. All peptides had identical net charge (+5) and amino acid composition, but different hydrophobicity and α-helical propensity. Peptide IG-19 suppressed LPS-induced cytokine/chemokine production by >90%, IG-19a and IG-19b suppressed it by 40−50%, and IG-19c and IG-19d did not suppress cytokine/chemokine production at all. In silico prediction algorithms and the peptide retention time (RT) on a C18 RP HPLC column indicated a linear association between α-helical propensity and hydrophobicity with the ability of the peptides to inhibit LPS-induced responses. Peptide RT exhibited a significant correlation (>70%) between the suppression of LPS-induced cytokine/chemokine production and peptide-induced production of the anti-inflammatory cytokine IL-1RA. These results indicate that RT on a C18 column can be used as a predictor for the immunomodulatory functions of cationic peptides. Overall, we demonstrated that the immunomodulatory functions of LL-37-derived peptides with identical positive charge and amino acid composition are directly associated with the predicted α-helical propensity and hydrophobicity of the peptides.https://www.mdpi.com/2218-273X/9/9/501cathelicidinLL-37IG-19α-helicityhydrophobicityinflammationimmunomodulationpeptide retention time |
| spellingShingle | Mahadevappa Hemshekhar Sana Faiyaz Ka-Yee Grace Choi Oleg V. Krokhin Neeloffer Mookherjee Immunomodulatory Functions of the Human Cathelicidin LL-37 (aa 13–31)-Derived Peptides are Associated with Predicted α-Helical Propensity and Hydrophobic Index Biomolecules cathelicidin LL-37 IG-19 α-helicity hydrophobicity inflammation immunomodulation peptide retention time |
| title | Immunomodulatory Functions of the Human Cathelicidin LL-37 (aa 13–31)-Derived Peptides are Associated with Predicted α-Helical Propensity and Hydrophobic Index |
| title_full | Immunomodulatory Functions of the Human Cathelicidin LL-37 (aa 13–31)-Derived Peptides are Associated with Predicted α-Helical Propensity and Hydrophobic Index |
| title_fullStr | Immunomodulatory Functions of the Human Cathelicidin LL-37 (aa 13–31)-Derived Peptides are Associated with Predicted α-Helical Propensity and Hydrophobic Index |
| title_full_unstemmed | Immunomodulatory Functions of the Human Cathelicidin LL-37 (aa 13–31)-Derived Peptides are Associated with Predicted α-Helical Propensity and Hydrophobic Index |
| title_short | Immunomodulatory Functions of the Human Cathelicidin LL-37 (aa 13–31)-Derived Peptides are Associated with Predicted α-Helical Propensity and Hydrophobic Index |
| title_sort | immunomodulatory functions of the human cathelicidin ll 37 aa 13 31 derived peptides are associated with predicted α helical propensity and hydrophobic index |
| topic | cathelicidin LL-37 IG-19 α-helicity hydrophobicity inflammation immunomodulation peptide retention time |
| url | https://www.mdpi.com/2218-273X/9/9/501 |
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