Mannan-Binding Lectin Suppresses Peptidoglycan-Induced TLR2 Activation and Inflammatory Responses
Peptidoglycan (PGN), as the major components of the bacterial cell wall, is known to cause excessive proinflammatory cytokine production. Toll-like receptor 2 (TLR2) is abundantly expressed on immune cells and has been shown to be involved in PGN-induced signaling. Although more and more evidences h...
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| Format: | Article |
| Language: | English |
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Wiley
2019-01-01
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| Series: | Mediators of Inflammation |
| Online Access: | http://dx.doi.org/10.1155/2019/1349784 |
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| _version_ | 1832552202550378496 |
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| author | Fanping Wang Yanhua Li Can Yang Yonghui Mu Yan Wang Wei Zhang Yonghui Yang Chen Chen Shijun Song Zhifa Shen Wenjun Wang Junpeng Li Jingjing Zhai Kang Guo Ruili Sun Lili Yu Mingyong Wang |
| author_facet | Fanping Wang Yanhua Li Can Yang Yonghui Mu Yan Wang Wei Zhang Yonghui Yang Chen Chen Shijun Song Zhifa Shen Wenjun Wang Junpeng Li Jingjing Zhai Kang Guo Ruili Sun Lili Yu Mingyong Wang |
| author_sort | Fanping Wang |
| collection | DOAJ |
| description | Peptidoglycan (PGN), as the major components of the bacterial cell wall, is known to cause excessive proinflammatory cytokine production. Toll-like receptor 2 (TLR2) is abundantly expressed on immune cells and has been shown to be involved in PGN-induced signaling. Although more and more evidences have indicated that PGN is recognized by TLR2, the role of TLR2 PGN recognition is controversial. Mannan-binding lectin (MBL), a plasma C-type lectin, plays a key role in innate immunity. More and more evidences show that MBL could suppress the amplification of inflammatory signals. Whether MBL can alter PGN-elicited cellular responses through TLR2 in macrophages is still unknown, and possible mechanism underlying it should be investigated. In this study, we found that MBL significantly attenuated PGN-induced inflammatory cytokine production, including TNF-α and IL-6, in PMA-stimulated THP-1 cells at both mRNA and protein levels. The expression of TLR2 was strongly induced by PGN stimulation. Furthermore, the administration of TLR2-neutralized antibody effectively suppressed PGN-induced TNF-α and IL-6 expression. These results supplied the evidence that PGN from Saccharomyces cerevisiae could be recognized by TLR2. In addition, we also found that MBL decreased PGN-induced TLR2 expression and suppressed TLR2-mediated downstream signaling, including the phosphorylation of IκBα, nuclear translocation of NF-κBp65, and phosphorylation of MAPK p38 and ERK1/2. Administration of MBL alone did not have an effect on the expression of TLR2. Finally, our data showed that PGN-mediated immune responses were more severely suppressed by preincubation with MBL and indicated that MBL can combine with both TLR2 and PGN to block the inflammation cytokine expression induced by PGN. All these data suggest that MBL could downregulate inflammation by modulating PGN/TLR2 signaling pathways. This study supports an important role for MBL in immune regulation and signaling pathways involved in inflammatory responses. |
| format | Article |
| id | doaj-art-0dd121e2bb0e4ee89b7fed8d6ed0d615 |
| institution | Kabale University |
| issn | 0962-9351 1466-1861 |
| language | English |
| publishDate | 2019-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Mediators of Inflammation |
| spelling | doaj-art-0dd121e2bb0e4ee89b7fed8d6ed0d6152025-02-03T05:59:09ZengWileyMediators of Inflammation0962-93511466-18612019-01-01201910.1155/2019/13497841349784Mannan-Binding Lectin Suppresses Peptidoglycan-Induced TLR2 Activation and Inflammatory ResponsesFanping Wang0Yanhua Li1Can Yang2Yonghui Mu3Yan Wang4Wei Zhang5Yonghui Yang6Chen Chen7Shijun Song8Zhifa Shen9Wenjun Wang10Junpeng Li11Jingjing Zhai12Kang Guo13Ruili Sun14Lili Yu15Mingyong Wang16School of Laboratory Medicine, Xinxiang Medical University, Xinxiang 453003, ChinaCollaborative Innovation Center of Molecular Diagnosis and Laboratory Medicine, Xinxiang 453003, ChinaCollaborative Innovation Center of Molecular Diagnosis and Laboratory Medicine, Xinxiang 453003, ChinaSchool of Basic Medical Sciences, Xinxiang Medical University, Xinxiang 453003, ChinaSchool of Laboratory Medicine, Xinxiang Medical University, Xinxiang 453003, ChinaSchool of Basic Medical Sciences, Xinxiang Medical University, Xinxiang 453003, ChinaSchool of Laboratory Medicine, Xinxiang Medical University, Xinxiang 453003, ChinaDepartment of Clinical Laboratory, The Third Affiliated Hospital of Xinxiang Medical University, Xinxiang, ChinaDepartment of Clinical Laboratory, The Third Affiliated Hospital of Xinxiang Medical University, Xinxiang, ChinaSchool of Laboratory Medicine, Xinxiang Medical University, Xinxiang 453003, ChinaState Key Laboratory of Respiratory Diseases, Center for Translational Medicine, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510120, ChinaDepartment of Clinical Laboratory, The Third Affiliated Hospital of Xinxiang Medical University, Xinxiang, ChinaDepartment of Laboratory Medicine, Women and Infants Hospital of Zhengzhou, Zhengzhou 450012, ChinaDepartment of Clinical Laboratory, The Third Affiliated Hospital of Xinxiang Medical University, Xinxiang, ChinaSchool of Laboratory Medicine, Xinxiang Medical University, Xinxiang 453003, ChinaCollaborative Innovation Center of Molecular Diagnosis and Laboratory Medicine, Xinxiang 453003, ChinaSchool of Laboratory Medicine, Xinxiang Medical University, Xinxiang 453003, ChinaPeptidoglycan (PGN), as the major components of the bacterial cell wall, is known to cause excessive proinflammatory cytokine production. Toll-like receptor 2 (TLR2) is abundantly expressed on immune cells and has been shown to be involved in PGN-induced signaling. Although more and more evidences have indicated that PGN is recognized by TLR2, the role of TLR2 PGN recognition is controversial. Mannan-binding lectin (MBL), a plasma C-type lectin, plays a key role in innate immunity. More and more evidences show that MBL could suppress the amplification of inflammatory signals. Whether MBL can alter PGN-elicited cellular responses through TLR2 in macrophages is still unknown, and possible mechanism underlying it should be investigated. In this study, we found that MBL significantly attenuated PGN-induced inflammatory cytokine production, including TNF-α and IL-6, in PMA-stimulated THP-1 cells at both mRNA and protein levels. The expression of TLR2 was strongly induced by PGN stimulation. Furthermore, the administration of TLR2-neutralized antibody effectively suppressed PGN-induced TNF-α and IL-6 expression. These results supplied the evidence that PGN from Saccharomyces cerevisiae could be recognized by TLR2. In addition, we also found that MBL decreased PGN-induced TLR2 expression and suppressed TLR2-mediated downstream signaling, including the phosphorylation of IκBα, nuclear translocation of NF-κBp65, and phosphorylation of MAPK p38 and ERK1/2. Administration of MBL alone did not have an effect on the expression of TLR2. Finally, our data showed that PGN-mediated immune responses were more severely suppressed by preincubation with MBL and indicated that MBL can combine with both TLR2 and PGN to block the inflammation cytokine expression induced by PGN. All these data suggest that MBL could downregulate inflammation by modulating PGN/TLR2 signaling pathways. This study supports an important role for MBL in immune regulation and signaling pathways involved in inflammatory responses.http://dx.doi.org/10.1155/2019/1349784 |
| spellingShingle | Fanping Wang Yanhua Li Can Yang Yonghui Mu Yan Wang Wei Zhang Yonghui Yang Chen Chen Shijun Song Zhifa Shen Wenjun Wang Junpeng Li Jingjing Zhai Kang Guo Ruili Sun Lili Yu Mingyong Wang Mannan-Binding Lectin Suppresses Peptidoglycan-Induced TLR2 Activation and Inflammatory Responses Mediators of Inflammation |
| title | Mannan-Binding Lectin Suppresses Peptidoglycan-Induced TLR2 Activation and Inflammatory Responses |
| title_full | Mannan-Binding Lectin Suppresses Peptidoglycan-Induced TLR2 Activation and Inflammatory Responses |
| title_fullStr | Mannan-Binding Lectin Suppresses Peptidoglycan-Induced TLR2 Activation and Inflammatory Responses |
| title_full_unstemmed | Mannan-Binding Lectin Suppresses Peptidoglycan-Induced TLR2 Activation and Inflammatory Responses |
| title_short | Mannan-Binding Lectin Suppresses Peptidoglycan-Induced TLR2 Activation and Inflammatory Responses |
| title_sort | mannan binding lectin suppresses peptidoglycan induced tlr2 activation and inflammatory responses |
| url | http://dx.doi.org/10.1155/2019/1349784 |
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