Curdlan (<i>Alcaligenes faecalis</i>) (1→3)-β-<span style="font-variant: small-caps">d</span>-Glucan Oligosaccharides Drive M1 Phenotype Polarization in Murine Bone Marrow-Derived Macrophages via Activation of MAPKs and NF-κB Pathways
Functional oligosaccharides, particularly curdlan (1→3)-β-<span style="font-variant: small-caps;">d</span>-glucan oligosaccharides (GOS), play important roles in modulating host immune responses. However, the molecular mechanisms underlying the immunostimulat...
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MDPI AG
2019-11-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/24/23/4251 |
| _version_ | 1817987906143256576 |
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| author | Jun Liu Jiqing Tang Xiuting Li Qiaojuan Yan Junwen Ma Zhengqiang Jiang |
| author_facet | Jun Liu Jiqing Tang Xiuting Li Qiaojuan Yan Junwen Ma Zhengqiang Jiang |
| author_sort | Jun Liu |
| collection | DOAJ |
| description | Functional oligosaccharides, particularly curdlan (1→3)-β-<span style="font-variant: small-caps;">d</span>-glucan oligosaccharides (GOS), play important roles in modulating host immune responses. However, the molecular mechanisms underlying the immunostimulatory effects of GOS on macrophage polarization are not clear. In this work, GOS (5−1000 µg/mL) were non-toxic to bone marrow-derived macrophages (BMDMs) with improved pinocytic and bactericidal capacities. Incubation with GOS (100 µg/mL) induced M1 phenotype polarization of BMDMs as evidenced by increased CD11c<sup>+</sup>/CD86<sup>+</sup> (10.1%) and M1 gene expression of inducible nitric oxide synthase, interleukin (IL)-1β, and chemokine C-C-motif ligand 2. Accordingly, the secretion of cytokines IL-1β, IL-6, monocyte chemotactic protein-1, and tumor necrosis factor-α, as well as the nitrite release of BMDMs were increased by GOS (100 µg/mL). Expression of mitogen-activated protein kinases (MAPKs) of phosphorylated (p)-c-Jun amino-terminal kinase, p-extracellular signal regulated kinase, and p-p38 in BMDMs were increased by GOS, as well as the p-Stat1. Moreover, nuclear factor-kappa B (NF-κB) p-p65 expression in BMDMs was promoted by GOS while it suppressed IκBα expression. Receptor blocking with anti-CR3 (CD11b/CD18) and anti-toll-like receptor (TLR) 2 antibodies diminished GOS induced M1 phenotype polarization with reduced mRNA expression of M1 genes, decreased cytokine and nitrite releases, and suppressed signaling pathway activation. Thus, CR3 (CD11b/CD18) and TLR2 mediated activation of MAPKs and NF-κB pathways are responsible for GOS induced polarization of BMDMs. |
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| language | English |
| last_indexed | 2024-04-14T00:28:15Z |
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| series | Molecules |
| spelling | doaj.art-4d30c186f3574a2cb42556d2318600622022-12-22T02:22:39ZengMDPI AGMolecules1420-30492019-11-012423425110.3390/molecules24234251molecules24234251Curdlan (<i>Alcaligenes faecalis</i>) (1→3)-β-<span style="font-variant: small-caps">d</span>-Glucan Oligosaccharides Drive M1 Phenotype Polarization in Murine Bone Marrow-Derived Macrophages via Activation of MAPKs and NF-κB PathwaysJun Liu0Jiqing Tang1Xiuting Li2Qiaojuan Yan3Junwen Ma4Zhengqiang Jiang5Beijing Advanced Innovation Center for Food Nutrition and Human Health, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, ChinaBeijing Advanced Innovation Center for Food Nutrition and Human Health, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, ChinaBeijing Advanced Innovation Center for Food Nutrition and Human Health, Beijing Technology and Business University, Beijing 100048, ChinaBioresource Utilization Laboratory, College of Engineering, China Agricultural University, Beijing 100083, ChinaBeijing Advanced Innovation Center for Food Nutrition and Human Health, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, ChinaBeijing Advanced Innovation Center for Food Nutrition and Human Health, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, ChinaFunctional oligosaccharides, particularly curdlan (1→3)-β-<span style="font-variant: small-caps;">d</span>-glucan oligosaccharides (GOS), play important roles in modulating host immune responses. However, the molecular mechanisms underlying the immunostimulatory effects of GOS on macrophage polarization are not clear. In this work, GOS (5−1000 µg/mL) were non-toxic to bone marrow-derived macrophages (BMDMs) with improved pinocytic and bactericidal capacities. Incubation with GOS (100 µg/mL) induced M1 phenotype polarization of BMDMs as evidenced by increased CD11c<sup>+</sup>/CD86<sup>+</sup> (10.1%) and M1 gene expression of inducible nitric oxide synthase, interleukin (IL)-1β, and chemokine C-C-motif ligand 2. Accordingly, the secretion of cytokines IL-1β, IL-6, monocyte chemotactic protein-1, and tumor necrosis factor-α, as well as the nitrite release of BMDMs were increased by GOS (100 µg/mL). Expression of mitogen-activated protein kinases (MAPKs) of phosphorylated (p)-c-Jun amino-terminal kinase, p-extracellular signal regulated kinase, and p-p38 in BMDMs were increased by GOS, as well as the p-Stat1. Moreover, nuclear factor-kappa B (NF-κB) p-p65 expression in BMDMs was promoted by GOS while it suppressed IκBα expression. Receptor blocking with anti-CR3 (CD11b/CD18) and anti-toll-like receptor (TLR) 2 antibodies diminished GOS induced M1 phenotype polarization with reduced mRNA expression of M1 genes, decreased cytokine and nitrite releases, and suppressed signaling pathway activation. Thus, CR3 (CD11b/CD18) and TLR2 mediated activation of MAPKs and NF-κB pathways are responsible for GOS induced polarization of BMDMs.https://www.mdpi.com/1420-3049/24/23/4251curdlan (1→3)-β-<span style="font-variant: small-caps">d</span>-glucan oligosaccharidesmacrophage polarizationmitogen-activated protein kinasesnuclear factor-kappa breceptor blocking |
| spellingShingle | Jun Liu Jiqing Tang Xiuting Li Qiaojuan Yan Junwen Ma Zhengqiang Jiang Curdlan (<i>Alcaligenes faecalis</i>) (1→3)-β-<span style="font-variant: small-caps">d</span>-Glucan Oligosaccharides Drive M1 Phenotype Polarization in Murine Bone Marrow-Derived Macrophages via Activation of MAPKs and NF-κB Pathways Molecules curdlan (1→3)-β-<span style="font-variant: small-caps">d</span>-glucan oligosaccharides macrophage polarization mitogen-activated protein kinases nuclear factor-kappa b receptor blocking |
| title | Curdlan (<i>Alcaligenes faecalis</i>) (1→3)-β-<span style="font-variant: small-caps">d</span>-Glucan Oligosaccharides Drive M1 Phenotype Polarization in Murine Bone Marrow-Derived Macrophages via Activation of MAPKs and NF-κB Pathways |
| title_full | Curdlan (<i>Alcaligenes faecalis</i>) (1→3)-β-<span style="font-variant: small-caps">d</span>-Glucan Oligosaccharides Drive M1 Phenotype Polarization in Murine Bone Marrow-Derived Macrophages via Activation of MAPKs and NF-κB Pathways |
| title_fullStr | Curdlan (<i>Alcaligenes faecalis</i>) (1→3)-β-<span style="font-variant: small-caps">d</span>-Glucan Oligosaccharides Drive M1 Phenotype Polarization in Murine Bone Marrow-Derived Macrophages via Activation of MAPKs and NF-κB Pathways |
| title_full_unstemmed | Curdlan (<i>Alcaligenes faecalis</i>) (1→3)-β-<span style="font-variant: small-caps">d</span>-Glucan Oligosaccharides Drive M1 Phenotype Polarization in Murine Bone Marrow-Derived Macrophages via Activation of MAPKs and NF-κB Pathways |
| title_short | Curdlan (<i>Alcaligenes faecalis</i>) (1→3)-β-<span style="font-variant: small-caps">d</span>-Glucan Oligosaccharides Drive M1 Phenotype Polarization in Murine Bone Marrow-Derived Macrophages via Activation of MAPKs and NF-κB Pathways |
| title_sort | curdlan i alcaligenes faecalis i 1 3 β span style font variant small caps d span glucan oligosaccharides drive m1 phenotype polarization in murine bone marrow derived macrophages via activation of mapks and nf κb pathways |
| topic | curdlan (1→3)-β-<span style="font-variant: small-caps">d</span>-glucan oligosaccharides macrophage polarization mitogen-activated protein kinases nuclear factor-kappa b receptor blocking |
| url | https://www.mdpi.com/1420-3049/24/23/4251 |
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