Chensinin-1b Alleviates DSS-Induced Inflammatory Bowel Disease by Inducing Macrophage Switching from the M1 to the M2 Phenotype
Inflammatory bowel disease (IBD) is a chronic relapsing inflammatory disorder with an increasing prevalence worldwide. Macrophage polarization is involved in the pathogenesis of IBD. Repolarization of macrophage has thus emerged as a novel therapeutic approach for managing IBD. Chensinin-1b, derived...
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MDPI AG
2024-02-01
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| author | Yue Sun Huiyu Li Xingpeng Duan Xiaoxiao Ma Chenxi Liu Dejing Shang |
| author_facet | Yue Sun Huiyu Li Xingpeng Duan Xiaoxiao Ma Chenxi Liu Dejing Shang |
| author_sort | Yue Sun |
| collection | DOAJ |
| description | Inflammatory bowel disease (IBD) is a chronic relapsing inflammatory disorder with an increasing prevalence worldwide. Macrophage polarization is involved in the pathogenesis of IBD. Repolarization of macrophage has thus emerged as a novel therapeutic approach for managing IBD. Chensinin-1b, derived from the skin of <i>Rana chensinensis</i>, is a derivative of a native antimicrobial peptide (AMP). It shows anti-inflammatory effects in sepsis models and can potentially modulate macrophage polarization. The objective of this research was to study the role of chensinin-1b in macrophage polarization and dextran sulfate sodium (DSS)-induced colitis. RAW264.7 macrophages were polarized to the M1 phenotype using lipopolysaccharide (LPS) and simultaneously administered chensinin-1b at various concentrations. The ability of chenisnin-1b to reorient macrophage polarization was assessed by ELISA, qRT-PCR, and flow cytometry analysis. The addition of chensinin-1b significantly restrained the expression of M1-associated proinflammatory cytokines and surface markers, including TNF-α, IL-6, NO, and CD86, and exaggerated the expression of M2-associated anti-inflammatory cytokines and surface markers, including IL-10, TGF-β1, <i>Arg-1</i>, <i>Fizz1</i>, <i>Chil3</i>, and CD206. Mechanistically, via Western Blotting, we revealed that chensinin-1b induces macrophage polarization from the M1 to the M2 phenotype by inhibiting the phosphorylation of nuclear factor-kappa B (NF-κB) and mitogen-activated protein kinase (MAPK). In mouse models of colitis, intraperitoneal administration of chensinin-1b alleviated symptoms induced by DSS, including weight loss, elevated disease activity index (DAI) scores, colon shortening, colonic tissue damage, and splenomegaly. Consistent with our in vitro data, chensinin-1b induced significant decreases in the expression of M1 phenotype biomarkers and increases in the expression of M2 phenotype biomarkers in the mouse colitis model. Furthermore, chensinin-1b treatment repressesed NF-κB phosphorylation in vivo. Overall, our data showed that chensinin-1b attenuates IBD by repolarizing macrophages from the M1 to the M2 phenotype, suggesting its potential as a therapeutic candidate for IBD. |
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| language | English |
| last_indexed | 2024-03-07T22:41:31Z |
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| spelling | doaj.art-3ee61aa1f2c34049a64378003ee1a67c2024-02-23T15:08:33ZengMDPI AGBiomedicines2227-90592024-02-0112234510.3390/biomedicines12020345Chensinin-1b Alleviates DSS-Induced Inflammatory Bowel Disease by Inducing Macrophage Switching from the M1 to the M2 PhenotypeYue Sun0Huiyu Li1Xingpeng Duan2Xiaoxiao Ma3Chenxi Liu4Dejing Shang5School of Life Science, Liaoning Normal University, Dalian 116081, ChinaSchool of Life Science, Liaoning Normal University, Dalian 116081, ChinaSchool of Life Science, Liaoning Normal University, Dalian 116081, ChinaSchool of Life Science, Liaoning Normal University, Dalian 116081, ChinaSchool of Life Science, Liaoning Normal University, Dalian 116081, ChinaSchool of Life Science, Liaoning Normal University, Dalian 116081, ChinaInflammatory bowel disease (IBD) is a chronic relapsing inflammatory disorder with an increasing prevalence worldwide. Macrophage polarization is involved in the pathogenesis of IBD. Repolarization of macrophage has thus emerged as a novel therapeutic approach for managing IBD. Chensinin-1b, derived from the skin of <i>Rana chensinensis</i>, is a derivative of a native antimicrobial peptide (AMP). It shows anti-inflammatory effects in sepsis models and can potentially modulate macrophage polarization. The objective of this research was to study the role of chensinin-1b in macrophage polarization and dextran sulfate sodium (DSS)-induced colitis. RAW264.7 macrophages were polarized to the M1 phenotype using lipopolysaccharide (LPS) and simultaneously administered chensinin-1b at various concentrations. The ability of chenisnin-1b to reorient macrophage polarization was assessed by ELISA, qRT-PCR, and flow cytometry analysis. The addition of chensinin-1b significantly restrained the expression of M1-associated proinflammatory cytokines and surface markers, including TNF-α, IL-6, NO, and CD86, and exaggerated the expression of M2-associated anti-inflammatory cytokines and surface markers, including IL-10, TGF-β1, <i>Arg-1</i>, <i>Fizz1</i>, <i>Chil3</i>, and CD206. Mechanistically, via Western Blotting, we revealed that chensinin-1b induces macrophage polarization from the M1 to the M2 phenotype by inhibiting the phosphorylation of nuclear factor-kappa B (NF-κB) and mitogen-activated protein kinase (MAPK). In mouse models of colitis, intraperitoneal administration of chensinin-1b alleviated symptoms induced by DSS, including weight loss, elevated disease activity index (DAI) scores, colon shortening, colonic tissue damage, and splenomegaly. Consistent with our in vitro data, chensinin-1b induced significant decreases in the expression of M1 phenotype biomarkers and increases in the expression of M2 phenotype biomarkers in the mouse colitis model. Furthermore, chensinin-1b treatment repressesed NF-κB phosphorylation in vivo. Overall, our data showed that chensinin-1b attenuates IBD by repolarizing macrophages from the M1 to the M2 phenotype, suggesting its potential as a therapeutic candidate for IBD.https://www.mdpi.com/2227-9059/12/2/345antimicrobial peptidemacrophage polarizationinflammatory bowel diseaseNF-κB |
| spellingShingle | Yue Sun Huiyu Li Xingpeng Duan Xiaoxiao Ma Chenxi Liu Dejing Shang Chensinin-1b Alleviates DSS-Induced Inflammatory Bowel Disease by Inducing Macrophage Switching from the M1 to the M2 Phenotype Biomedicines antimicrobial peptide macrophage polarization inflammatory bowel disease NF-κB |
| title | Chensinin-1b Alleviates DSS-Induced Inflammatory Bowel Disease by Inducing Macrophage Switching from the M1 to the M2 Phenotype |
| title_full | Chensinin-1b Alleviates DSS-Induced Inflammatory Bowel Disease by Inducing Macrophage Switching from the M1 to the M2 Phenotype |
| title_fullStr | Chensinin-1b Alleviates DSS-Induced Inflammatory Bowel Disease by Inducing Macrophage Switching from the M1 to the M2 Phenotype |
| title_full_unstemmed | Chensinin-1b Alleviates DSS-Induced Inflammatory Bowel Disease by Inducing Macrophage Switching from the M1 to the M2 Phenotype |
| title_short | Chensinin-1b Alleviates DSS-Induced Inflammatory Bowel Disease by Inducing Macrophage Switching from the M1 to the M2 Phenotype |
| title_sort | chensinin 1b alleviates dss induced inflammatory bowel disease by inducing macrophage switching from the m1 to the m2 phenotype |
| topic | antimicrobial peptide macrophage polarization inflammatory bowel disease NF-κB |
| url | https://www.mdpi.com/2227-9059/12/2/345 |
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