<i>Chlorella pyrenoidosa</i> Polysaccharide CPP-3a Promotes M1 Polarization of Macrophages via TLR4/2-MyD88-NF-κB/p38 MAPK Signaling Pathways
The immunomodulatory polysaccharide CPP-3a, purified from <i>Chlorella pyrenoidosa</i>, was investigated for its effects on RAW264.7 macrophages and underlying mechanisms, revealing that CPP-3a significantly enhanced phagocytic capacity and nitric oxide production while upregulating pro-...
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| Language: | English |
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2025-07-01
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| Series: | Marine Drugs |
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| Online Access: | https://www.mdpi.com/1660-3397/23/7/290 |
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| author | Yihua Pi Qingxia Yuan Shaoting Qin Chundie Lan Qingdong Nong Chenxia Yun Haibo Tang Jing Leng Jian Xiao Longyan Zhao Lifeng Zhang |
| author_facet | Yihua Pi Qingxia Yuan Shaoting Qin Chundie Lan Qingdong Nong Chenxia Yun Haibo Tang Jing Leng Jian Xiao Longyan Zhao Lifeng Zhang |
| author_sort | Yihua Pi |
| collection | DOAJ |
| description | The immunomodulatory polysaccharide CPP-3a, purified from <i>Chlorella pyrenoidosa</i>, was investigated for its effects on RAW264.7 macrophages and underlying mechanisms, revealing that CPP-3a significantly enhanced phagocytic capacity and nitric oxide production while upregulating pro-inflammatory cytokines TNF-α and IL-6 and elevating the co-stimulatory molecule CD86, collectively driving robust M1 polarization. Mechanistically, TLR4-, TLR2-specific inhibitors, and TLR4-knockout cells confirmed TLR4 as the primary receptor for CPP-3a, with TLR2 playing a secondary role in cytokine modulation. CPP-3a activated NF-κB and p38 MAPK signaling pathways via the MyD88-dependent pathway, evidenced by phosphorylation of NF-κB/p65 with its nuclear translocation and increased phosphorylation of p38 MAPK, with these signaling activations further validated by specific pathway inhibitors that abolished M1 polarization phenotypes. Collectively, CPP-3a emerges as a potent TLR4-targeted immunomodulator with adjuvant potential for inflammatory and infectious diseases. |
| format | Article |
| id | doaj-art-78df63d30809428c934b4b9f1014a044 |
| institution | Kabale University |
| issn | 1660-3397 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Marine Drugs |
| spelling | doaj-art-78df63d30809428c934b4b9f1014a0442025-08-20T03:32:27ZengMDPI AGMarine Drugs1660-33972025-07-0123729010.3390/md23070290<i>Chlorella pyrenoidosa</i> Polysaccharide CPP-3a Promotes M1 Polarization of Macrophages via TLR4/2-MyD88-NF-κB/p38 MAPK Signaling PathwaysYihua Pi0Qingxia Yuan1Shaoting Qin2Chundie Lan3Qingdong Nong4Chenxia Yun5Haibo Tang6Jing Leng7Jian Xiao8Longyan Zhao9Lifeng Zhang10Guangxi Key Laboratory of Translational Medicine for Treating High-Incidence Infectious Diseases with Integrative Medicine, Guangxi University of Chinese Medicine, Nanning 530200, ChinaGuangxi Key Laboratory of Marine Drugs, University Engineering Research Center of High-Efficient Utilization of Marine Traditional Chinese Medicine Resources, Institute of Marine Drugs, University of Chinese Medicine, Nanning 530200, ChinaGuangxi Key Laboratory of Translational Medicine for Treating High-Incidence Infectious Diseases with Integrative Medicine, Guangxi University of Chinese Medicine, Nanning 530200, ChinaGuangxi Key Laboratory of Translational Medicine for Treating High-Incidence Infectious Diseases with Integrative Medicine, Guangxi University of Chinese Medicine, Nanning 530200, ChinaGuangxi Key Laboratory of Translational Medicine for Treating High-Incidence Infectious Diseases with Integrative Medicine, Guangxi University of Chinese Medicine, Nanning 530200, ChinaGuangxi Key Laboratory of Translational Medicine for Treating High-Incidence Infectious Diseases with Integrative Medicine, Guangxi University of Chinese Medicine, Nanning 530200, ChinaGuangxi Key Laboratory of Translational Medicine for Treating High-Incidence Infectious Diseases with Integrative Medicine, Guangxi University of Chinese Medicine, Nanning 530200, ChinaGuangxi Key Laboratory of Translational Medicine for Treating High-Incidence Infectious Diseases with Integrative Medicine, Guangxi University of Chinese Medicine, Nanning 530200, ChinaGuangxi Key Laboratory of Translational Medicine for Treating High-Incidence Infectious Diseases with Integrative Medicine, Guangxi University of Chinese Medicine, Nanning 530200, ChinaGuangxi Key Laboratory of Marine Drugs, University Engineering Research Center of High-Efficient Utilization of Marine Traditional Chinese Medicine Resources, Institute of Marine Drugs, University of Chinese Medicine, Nanning 530200, ChinaGuangxi Key Laboratory of Translational Medicine for Treating High-Incidence Infectious Diseases with Integrative Medicine, Guangxi University of Chinese Medicine, Nanning 530200, ChinaThe immunomodulatory polysaccharide CPP-3a, purified from <i>Chlorella pyrenoidosa</i>, was investigated for its effects on RAW264.7 macrophages and underlying mechanisms, revealing that CPP-3a significantly enhanced phagocytic capacity and nitric oxide production while upregulating pro-inflammatory cytokines TNF-α and IL-6 and elevating the co-stimulatory molecule CD86, collectively driving robust M1 polarization. Mechanistically, TLR4-, TLR2-specific inhibitors, and TLR4-knockout cells confirmed TLR4 as the primary receptor for CPP-3a, with TLR2 playing a secondary role in cytokine modulation. CPP-3a activated NF-κB and p38 MAPK signaling pathways via the MyD88-dependent pathway, evidenced by phosphorylation of NF-κB/p65 with its nuclear translocation and increased phosphorylation of p38 MAPK, with these signaling activations further validated by specific pathway inhibitors that abolished M1 polarization phenotypes. Collectively, CPP-3a emerges as a potent TLR4-targeted immunomodulator with adjuvant potential for inflammatory and infectious diseases.https://www.mdpi.com/1660-3397/23/7/290<i>Chlorella</i> polysaccharidemacrophageM1 polarizationTLR4NF-κB |
| spellingShingle | Yihua Pi Qingxia Yuan Shaoting Qin Chundie Lan Qingdong Nong Chenxia Yun Haibo Tang Jing Leng Jian Xiao Longyan Zhao Lifeng Zhang <i>Chlorella pyrenoidosa</i> Polysaccharide CPP-3a Promotes M1 Polarization of Macrophages via TLR4/2-MyD88-NF-κB/p38 MAPK Signaling Pathways Marine Drugs <i>Chlorella</i> polysaccharide macrophage M1 polarization TLR4 NF-κB |
| title | <i>Chlorella pyrenoidosa</i> Polysaccharide CPP-3a Promotes M1 Polarization of Macrophages via TLR4/2-MyD88-NF-κB/p38 MAPK Signaling Pathways |
| title_full | <i>Chlorella pyrenoidosa</i> Polysaccharide CPP-3a Promotes M1 Polarization of Macrophages via TLR4/2-MyD88-NF-κB/p38 MAPK Signaling Pathways |
| title_fullStr | <i>Chlorella pyrenoidosa</i> Polysaccharide CPP-3a Promotes M1 Polarization of Macrophages via TLR4/2-MyD88-NF-κB/p38 MAPK Signaling Pathways |
| title_full_unstemmed | <i>Chlorella pyrenoidosa</i> Polysaccharide CPP-3a Promotes M1 Polarization of Macrophages via TLR4/2-MyD88-NF-κB/p38 MAPK Signaling Pathways |
| title_short | <i>Chlorella pyrenoidosa</i> Polysaccharide CPP-3a Promotes M1 Polarization of Macrophages via TLR4/2-MyD88-NF-κB/p38 MAPK Signaling Pathways |
| title_sort | i chlorella pyrenoidosa i polysaccharide cpp 3a promotes m1 polarization of macrophages via tlr4 2 myd88 nf κb p38 mapk signaling pathways |
| topic | <i>Chlorella</i> polysaccharide macrophage M1 polarization TLR4 NF-κB |
| url | https://www.mdpi.com/1660-3397/23/7/290 |
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