{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T14:54:50Z","timestamp":1787756090479,"version":"build-2784847793"},"reference-count":54,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2023,4,19]],"date-time":"2023-04-19T00:00:00Z","timestamp":1681862400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Minist\u00e8re de l\u2019Enseignement Sup\u00e9rieur et de la Recherche Scientifique","award":["PHC-Utique 21G0819"],"award-info":[{"award-number":["PHC-Utique 21G0819"]}]},{"name":"Institut Pasteur de Tunis","award":["PHC-Utique 21G0819"],"award-info":[{"award-number":["PHC-Utique 21G0819"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxins"],"abstract":"<jats:p>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-\u03b1, 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-\u03b1 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.<\/jats:p>","DOI":"10.3390\/toxins15040298","type":"journal-article","created":{"date-parts":[[2023,4,20]],"date-time":"2023-04-20T02:01:11Z","timestamp":1681956071000},"page":"298","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Natriuretic-like Peptide Lebetin 2 Mediates M2 Macrophage Polarization in LPS-Activated RAW264.7 Cells in an IL-10-Dependent Manner"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1195-6043","authenticated-orcid":false,"given":"Dorsaf","family":"Bouzazi","sequence":"first","affiliation":[{"name":"Plateforme de Physiologie et Physiopathologie Cardiovasculaires (P2C), Laboratoire des Biomol\u00e9cules, Venins et Applications Th\u00e9ranostiques (LR20IPT01), Institut Pasteur de Tunis, Universit\u00e9 Tunis El Manar, Tunis 1068, Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wael","family":"Mami","sequence":"additional","affiliation":[{"name":"Plateforme de Physiologie et Physiopathologie Cardiovasculaires (P2C), Laboratoire des Biomol\u00e9cules, Venins et Applications Th\u00e9ranostiques (LR20IPT01), Institut Pasteur de Tunis, Universit\u00e9 Tunis El Manar, Tunis 1068, Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5642-8805","authenticated-orcid":false,"given":"Amor","family":"Mosbah","sequence":"additional","affiliation":[{"name":"Laboratory of Biotechnology and Bio-Geo Resources Valorization (LR11ES31), Higher Institute of Biotechnology of Sidi Thabet (ISBST), University of Manouba, Tunis 2010, Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naziha","family":"Marrakchi","sequence":"additional","affiliation":[{"name":"Plateforme de Physiologie et Physiopathologie Cardiovasculaires (P2C), Laboratoire des Biomol\u00e9cules, Venins et Applications Th\u00e9ranostiques (LR20IPT01), Institut Pasteur de Tunis, Universit\u00e9 Tunis El Manar, Tunis 1068, Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melika","family":"Ben Ahmed","sequence":"additional","affiliation":[{"name":"Laboratoire de Transmission, Department of Clinical Immunology, Contr\u00f4le et Immunobiologie des Infections, Institut Pasteur de Tunis, Universit\u00e9 Tunis El Manar, Tunis 1068, Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erij","family":"Messadi","sequence":"additional","affiliation":[{"name":"Plateforme de Physiologie et Physiopathologie Cardiovasculaires (P2C), Laboratoire des Biomol\u00e9cules, Venins et Applications Th\u00e9ranostiques (LR20IPT01), Institut Pasteur de Tunis, Universit\u00e9 Tunis El Manar, Tunis 1068, Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,4,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Tourki, B., Dumesnil, A., Belaidi, E., Ghrir, S., Godin-Ribuot, D., Marrakchi, N., Richard, V., Mulder, P., and Messadi, E. 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