Natriuretic-like Peptide Lebetin 2 Mediates M2 Macrophage Polarization in LPS-Activated RAW264.7 Cells in an IL-10-Dependent Manner
Snake natriuretic peptide (NP) Lebetin 2 (L2) has been shown to improve cardiac function and reduce fibrosis as well as inflammation by promoting M2-type macrophages in a reperfused myocardial infarction (MI) model. However, the inflammatory mechanism of L2 remains unclear. Therefore, we investigate...
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MDPI AG
2023-04-01
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| Series: | Toxins |
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| Online Access: | https://www.mdpi.com/2072-6651/15/4/298 |
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| author | Dorsaf Bouzazi Wael Mami Amor Mosbah Naziha Marrakchi Melika Ben Ahmed Erij Messadi |
| author_facet | Dorsaf Bouzazi Wael Mami Amor Mosbah Naziha Marrakchi Melika Ben Ahmed Erij Messadi |
| author_sort | Dorsaf Bouzazi |
| collection | DOAJ |
| description | Snake natriuretic peptide (NP) Lebetin 2 (L2) has been shown to improve cardiac function and reduce fibrosis as well as inflammation by promoting M2-type macrophages in a reperfused myocardial infarction (MI) model. However, the inflammatory mechanism of L2 remains unclear. Therefore, we investigated the effect of L2 on macrophage polarization in lipopolysaccharide (LPS)-activated RAW264.7 cells in vitro and explored the associated underlying mechanisms. TNF-α, IL-6 and IL-10 levels were assessed using an ELISA assay, and M2 macrophage polarization was determined by flow cytometry. L2 was used at non-cytotoxic concentrations determined by a preliminary MTT cell viability assay, and compared to B-type natriuretic peptide (BNP). In LPS-activated cells, both peptides reduced TNF-α and IL-6 release compared to controls. However, only L2 increased IL-10 release in a sustained manner and promoted downstream M2 macrophage polarization. Pretreatment of LPS-activated RAW264.7 cells with the selective NP receptor (NPR) antagonist isatin abolished both IL-10 and M2-like macrophage potentiation provided by L2. In addition, cell pretreatment with the IL-10 inhibitor suppressed L2-induced M2 macrophage polarization. We conclude that L2 exerts an anti-inflammatory response to LPS by regulating the release of inflammatory cytokines via stimulating of NP receptors and promoting M2 macrophage polarization through activation of IL-10 signaling. |
| first_indexed | 2024-03-11T04:27:44Z |
| format | Article |
| id | doaj.art-08a7baed1b5047aa95cdc757ca1f866e |
| institution | Directory Open Access Journal |
| issn | 2072-6651 |
| language | English |
| last_indexed | 2024-03-11T04:27:44Z |
| publishDate | 2023-04-01 |
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| record_format | Article |
| series | Toxins |
| spelling | doaj.art-08a7baed1b5047aa95cdc757ca1f866e2023-11-17T21:39:13ZengMDPI AGToxins2072-66512023-04-0115429810.3390/toxins15040298Natriuretic-like Peptide Lebetin 2 Mediates M2 Macrophage Polarization in LPS-Activated RAW264.7 Cells in an IL-10-Dependent MannerDorsaf Bouzazi0Wael Mami1Amor Mosbah2Naziha Marrakchi3Melika Ben Ahmed4Erij Messadi5Plateforme de Physiologie et Physiopathologie Cardiovasculaires (P2C), Laboratoire des Biomolécules, Venins et Applications Théranostiques (LR20IPT01), Institut Pasteur de Tunis, Université Tunis El Manar, Tunis 1068, TunisiaPlateforme de Physiologie et Physiopathologie Cardiovasculaires (P2C), Laboratoire des Biomolécules, Venins et Applications Théranostiques (LR20IPT01), Institut Pasteur de Tunis, Université Tunis El Manar, Tunis 1068, TunisiaLaboratory of Biotechnology and Bio-Geo Resources Valorization (LR11ES31), Higher Institute of Biotechnology of Sidi Thabet (ISBST), University of Manouba, Tunis 2010, TunisiaPlateforme de Physiologie et Physiopathologie Cardiovasculaires (P2C), Laboratoire des Biomolécules, Venins et Applications Théranostiques (LR20IPT01), Institut Pasteur de Tunis, Université Tunis El Manar, Tunis 1068, TunisiaLaboratoire de Transmission, Department of Clinical Immunology, Contrôle et Immunobiologie des Infections, Institut Pasteur de Tunis, Université Tunis El Manar, Tunis 1068, TunisiaPlateforme de Physiologie et Physiopathologie Cardiovasculaires (P2C), Laboratoire des Biomolécules, Venins et Applications Théranostiques (LR20IPT01), Institut Pasteur de Tunis, Université Tunis El Manar, Tunis 1068, TunisiaSnake natriuretic peptide (NP) Lebetin 2 (L2) has been shown to improve cardiac function and reduce fibrosis as well as inflammation by promoting M2-type macrophages in a reperfused myocardial infarction (MI) model. However, the inflammatory mechanism of L2 remains unclear. Therefore, we investigated the effect of L2 on macrophage polarization in lipopolysaccharide (LPS)-activated RAW264.7 cells in vitro and explored the associated underlying mechanisms. TNF-α, IL-6 and IL-10 levels were assessed using an ELISA assay, and M2 macrophage polarization was determined by flow cytometry. L2 was used at non-cytotoxic concentrations determined by a preliminary MTT cell viability assay, and compared to B-type natriuretic peptide (BNP). In LPS-activated cells, both peptides reduced TNF-α and IL-6 release compared to controls. However, only L2 increased IL-10 release in a sustained manner and promoted downstream M2 macrophage polarization. Pretreatment of LPS-activated RAW264.7 cells with the selective NP receptor (NPR) antagonist isatin abolished both IL-10 and M2-like macrophage potentiation provided by L2. In addition, cell pretreatment with the IL-10 inhibitor suppressed L2-induced M2 macrophage polarization. We conclude that L2 exerts an anti-inflammatory response to LPS by regulating the release of inflammatory cytokines via stimulating of NP receptors and promoting M2 macrophage polarization through activation of IL-10 signaling.https://www.mdpi.com/2072-6651/15/4/298snake venom-derived natriuretic peptidelebetin 2inflammationcytokinesmacrophage polarizationinterleukin-10 |
| spellingShingle | Dorsaf Bouzazi Wael Mami Amor Mosbah Naziha Marrakchi Melika Ben Ahmed Erij Messadi Natriuretic-like Peptide Lebetin 2 Mediates M2 Macrophage Polarization in LPS-Activated RAW264.7 Cells in an IL-10-Dependent Manner Toxins snake venom-derived natriuretic peptide lebetin 2 inflammation cytokines macrophage polarization interleukin-10 |
| title | Natriuretic-like Peptide Lebetin 2 Mediates M2 Macrophage Polarization in LPS-Activated RAW264.7 Cells in an IL-10-Dependent Manner |
| title_full | Natriuretic-like Peptide Lebetin 2 Mediates M2 Macrophage Polarization in LPS-Activated RAW264.7 Cells in an IL-10-Dependent Manner |
| title_fullStr | Natriuretic-like Peptide Lebetin 2 Mediates M2 Macrophage Polarization in LPS-Activated RAW264.7 Cells in an IL-10-Dependent Manner |
| title_full_unstemmed | Natriuretic-like Peptide Lebetin 2 Mediates M2 Macrophage Polarization in LPS-Activated RAW264.7 Cells in an IL-10-Dependent Manner |
| title_short | Natriuretic-like Peptide Lebetin 2 Mediates M2 Macrophage Polarization in LPS-Activated RAW264.7 Cells in an IL-10-Dependent Manner |
| title_sort | natriuretic like peptide lebetin 2 mediates m2 macrophage polarization in lps activated raw264 7 cells in an il 10 dependent manner |
| topic | snake venom-derived natriuretic peptide lebetin 2 inflammation cytokines macrophage polarization interleukin-10 |
| url | https://www.mdpi.com/2072-6651/15/4/298 |
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