A Novel CD206 Targeting Peptide Inhibits Bleomycin-Induced Pulmonary Fibrosis in Mice
Activated M2-polarized macrophages are drivers of pulmonary fibrosis in several clinical scenarios, including Idiopathic Pulmonary Fibrosis (IPF). In this study, we investigated the effects of targeting the CD206 receptor in M2-like macrophages with a novel synthetic analogue of a naturally occurrin...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-04-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/12/9/1254 |
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| author | Anghesom Ghebremedhin Ahmad Bin Salam Benjamin Adu-Addai Steve Noonan Richard Stratton Md Shakir Uddin Ahmed Chandra Khantwal George R. Martin Huixian Lin Chris Andrews Balasubramanyam Karanam Udo Rudloff Henry Lopez Jesse Jaynes Clayton Yates |
| author_facet | Anghesom Ghebremedhin Ahmad Bin Salam Benjamin Adu-Addai Steve Noonan Richard Stratton Md Shakir Uddin Ahmed Chandra Khantwal George R. Martin Huixian Lin Chris Andrews Balasubramanyam Karanam Udo Rudloff Henry Lopez Jesse Jaynes Clayton Yates |
| author_sort | Anghesom Ghebremedhin |
| collection | DOAJ |
| description | Activated M2-polarized macrophages are drivers of pulmonary fibrosis in several clinical scenarios, including Idiopathic Pulmonary Fibrosis (IPF). In this study, we investigated the effects of targeting the CD206 receptor in M2-like macrophages with a novel synthetic analogue of a naturally occurring Host Defense Peptide (HDP), RP-832c, to decrease profibrotic cytokines. RP-832c selectively binds to CD206 on M2-polarized bone marrow-derived macrophages (BMDM) in vitro, resulting in a time-dependent decrease in CD206 expression and a transient increase in M1-macrophage marker TNF-α. To elucidate the antifibrotic effects of RP-832c, we used a murine model of bleomycin (BLM)-induced early-stage pulmonary fibrosis. RP-832c significantly reduced fibrosis in a dose-dependent manner, and decreased CD206, TGF-β1, and α-SMA expression in mouse lungs. Similarly, in an established model of lung fibrosis, RP-832c significantly decreased lung fibrosis and significantly decreased inflammatory cytokines TNF-α, IL-6, IL-10, IFN-γ, CXCL1/2, and fibrosis markers TGF-β1 and MMP-13. In comparison with the FDA-approved drugs Nintedanib and Pirfenidone, RP-832c exhibited a similar reduction in fibrosis compared to Pirfenidone, and to a greater extent than Nintedanib, with no apparent toxicities observed. In summary, our findings showed that inhibiting the profibrotic alternatively activated M2-like macrophages using a novel peptide, RP-832c, could reduce BLM-induced pulmonary fibrosis in mice, warranting the therapeutic potential of this peptide for patients with pulmonary fibrosis. |
| first_indexed | 2024-03-11T04:22:13Z |
| format | Article |
| id | doaj.art-634b487e00244c5a87f649e520e2e17c |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-11T04:22:13Z |
| publishDate | 2023-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-634b487e00244c5a87f649e520e2e17c2023-11-17T22:43:25ZengMDPI AGCells2073-44092023-04-01129125410.3390/cells12091254A Novel CD206 Targeting Peptide Inhibits Bleomycin-Induced Pulmonary Fibrosis in MiceAnghesom Ghebremedhin0Ahmad Bin Salam1Benjamin Adu-Addai2Steve Noonan3Richard Stratton4Md Shakir Uddin Ahmed5Chandra Khantwal6George R. Martin7Huixian Lin8Chris Andrews9Balasubramanyam Karanam10Udo Rudloff11Henry Lopez12Jesse Jaynes13Clayton Yates14Moores Cancer Center, University of California San Diego, La Jolla, CA 92093, USADepartment of Biology and Center for Cancer Research, Tuskegee University, Carver Research Foundation, Tuskegee, AL 36088, USADepartment of Pathobiology, College of Veterinary Medicine, Tuskegee University, Tuskegee, AL 36088, USAMurigenics Inc., 941 Railroad Ave., Vallejo, CA 94592, USARoyal Free Hospital, UCL Division of Medicine, University College London, London WC1E 6JF, UKDepartment of Biology and Center for Cancer Research, Tuskegee University, Carver Research Foundation, Tuskegee, AL 36088, USAMurigenics Inc., 941 Railroad Ave., Vallejo, CA 94592, USARiptide Bioscience, 941 Railroad Ave., Vallejo, CA 94592, USADepartment of Biology and Center for Cancer Research, Tuskegee University, Carver Research Foundation, Tuskegee, AL 36088, USADepartment of Biology and Center for Cancer Research, Tuskegee University, Carver Research Foundation, Tuskegee, AL 36088, USADepartment of Biology and Center for Cancer Research, Tuskegee University, Carver Research Foundation, Tuskegee, AL 36088, USARare Tumor Initiative, Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USAMurigenics Inc., 941 Railroad Ave., Vallejo, CA 94592, USACollege of Agriculture, Environment and Nutrition Sciences, Tuskegee University, Tuskegee, AL 36088, USADepartment of Biology and Center for Cancer Research, Tuskegee University, Carver Research Foundation, Tuskegee, AL 36088, USAActivated M2-polarized macrophages are drivers of pulmonary fibrosis in several clinical scenarios, including Idiopathic Pulmonary Fibrosis (IPF). In this study, we investigated the effects of targeting the CD206 receptor in M2-like macrophages with a novel synthetic analogue of a naturally occurring Host Defense Peptide (HDP), RP-832c, to decrease profibrotic cytokines. RP-832c selectively binds to CD206 on M2-polarized bone marrow-derived macrophages (BMDM) in vitro, resulting in a time-dependent decrease in CD206 expression and a transient increase in M1-macrophage marker TNF-α. To elucidate the antifibrotic effects of RP-832c, we used a murine model of bleomycin (BLM)-induced early-stage pulmonary fibrosis. RP-832c significantly reduced fibrosis in a dose-dependent manner, and decreased CD206, TGF-β1, and α-SMA expression in mouse lungs. Similarly, in an established model of lung fibrosis, RP-832c significantly decreased lung fibrosis and significantly decreased inflammatory cytokines TNF-α, IL-6, IL-10, IFN-γ, CXCL1/2, and fibrosis markers TGF-β1 and MMP-13. In comparison with the FDA-approved drugs Nintedanib and Pirfenidone, RP-832c exhibited a similar reduction in fibrosis compared to Pirfenidone, and to a greater extent than Nintedanib, with no apparent toxicities observed. In summary, our findings showed that inhibiting the profibrotic alternatively activated M2-like macrophages using a novel peptide, RP-832c, could reduce BLM-induced pulmonary fibrosis in mice, warranting the therapeutic potential of this peptide for patients with pulmonary fibrosis.https://www.mdpi.com/2073-4409/12/9/1254macrophagesmyofibroblastsIPFimmunotherapyCD206 |
| spellingShingle | Anghesom Ghebremedhin Ahmad Bin Salam Benjamin Adu-Addai Steve Noonan Richard Stratton Md Shakir Uddin Ahmed Chandra Khantwal George R. Martin Huixian Lin Chris Andrews Balasubramanyam Karanam Udo Rudloff Henry Lopez Jesse Jaynes Clayton Yates A Novel CD206 Targeting Peptide Inhibits Bleomycin-Induced Pulmonary Fibrosis in Mice Cells macrophages myofibroblasts IPF immunotherapy CD206 |
| title | A Novel CD206 Targeting Peptide Inhibits Bleomycin-Induced Pulmonary Fibrosis in Mice |
| title_full | A Novel CD206 Targeting Peptide Inhibits Bleomycin-Induced Pulmonary Fibrosis in Mice |
| title_fullStr | A Novel CD206 Targeting Peptide Inhibits Bleomycin-Induced Pulmonary Fibrosis in Mice |
| title_full_unstemmed | A Novel CD206 Targeting Peptide Inhibits Bleomycin-Induced Pulmonary Fibrosis in Mice |
| title_short | A Novel CD206 Targeting Peptide Inhibits Bleomycin-Induced Pulmonary Fibrosis in Mice |
| title_sort | novel cd206 targeting peptide inhibits bleomycin induced pulmonary fibrosis in mice |
| topic | macrophages myofibroblasts IPF immunotherapy CD206 |
| url | https://www.mdpi.com/2073-4409/12/9/1254 |
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