CD38 Deficiency Promotes Inflammatory Response through Activating Sirt1/NF-κB-Mediated Inhibition of TLR2 Expression in Macrophages
CD38 was first identified as a lymphocyte-specific antigen and then has been found to be widely expressed in a variety of cell types. The functions of CD38 are involved in numerous biological processes including immune responses. Here, we showed the downregulations of both TLR2 mRNA and protein in m...
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| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2018-01-01
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| Series: | Mediators of Inflammation |
| Online Access: | http://dx.doi.org/10.1155/2018/8736949 |
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| author | Yisong Qian Chuqiao Chen Leliang Ma Ziwei Wang Ling-Fang Wang Li Zuo Yaqin Yang Xiang Huang Meixiu Jiang Xiaolei Wang Huidong Shi Mingui Fu Ke-Yu Deng Hong-Bo Xin |
| author_facet | Yisong Qian Chuqiao Chen Leliang Ma Ziwei Wang Ling-Fang Wang Li Zuo Yaqin Yang Xiang Huang Meixiu Jiang Xiaolei Wang Huidong Shi Mingui Fu Ke-Yu Deng Hong-Bo Xin |
| author_sort | Yisong Qian |
| collection | DOAJ |
| description | CD38 was first identified as a lymphocyte-specific antigen and then has been found to be widely expressed in a variety of cell types. The functions of CD38 are involved in numerous biological processes including immune responses. Here, we showed the downregulations of both TLR2 mRNA and protein in macrophages from CD38−/− mice and in CD38 knockdown RAW264.7 cells. Several NF-κB-binding motifs in the promoter region of the TLR2 gene were identified by the bioinformatics analysis and were confirmed by the luciferase activity assay with the different truncated TLR2 promoters. CD38 deficiency resulted in the reduction of NF-κB p65 and acetyl-NF-κB p65 (Ac-p65) levels as determined by Western blot. The expression of Sirt1 did not change, but an increased activity of Sirt1 was observed in CD38-deficient macrophages. Inhibition of the Sirt1/NF-κB signaling pathway resulted in downregulation of TLR2 expression in RAW264.7 cells. However, re-expression of CD38 in the knockdown clones reversed the effect on Sirt1/NF-κB/TLR2 signaling, which is NAD-dependent. Moreover, the inflammatory cytokines including G-CSF, IL-1alpha, IL-6, MCP-1, MIP-1alpha, and RANTES were increased in CD38 knockdown RAW264.7 cells. Taken together, our data demonstrated that CD38 deficiency enhances inflammatory response in macrophages, and the mechanism may be partly associated with increased Sirt1 activity, which promoted NF-κB deacetylation and then inhibited expression of the TLR2 gene. Obviously, our study may provide an insight into the molecular mechanisms in CD38-mediated inflammation. |
| format | Article |
| id | doaj-art-8a56d059d2894866892a31d34b36294f |
| institution | Kabale University |
| issn | 0962-9351 1466-1861 |
| language | English |
| publishDate | 2018-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Mediators of Inflammation |
| spelling | doaj-art-8a56d059d2894866892a31d34b36294f2025-08-20T03:37:50ZengWileyMediators of Inflammation0962-93511466-18612018-01-01201810.1155/2018/87369498736949CD38 Deficiency Promotes Inflammatory Response through Activating Sirt1/NF-κB-Mediated Inhibition of TLR2 Expression in MacrophagesYisong Qian0Chuqiao Chen1Leliang Ma2Ziwei Wang3Ling-Fang Wang4Li Zuo5Yaqin Yang6Xiang Huang7Meixiu Jiang8Xiaolei Wang9Huidong Shi10Mingui Fu11Ke-Yu Deng12Hong-Bo Xin13Institute of Translational Medicine, Nanchang University, Nanchang 330031, ChinaInstitute of Translational Medicine, Nanchang University, Nanchang 330031, ChinaInstitute of Translational Medicine, Nanchang University, Nanchang 330031, ChinaInstitute of Translational Medicine, Nanchang University, Nanchang 330031, ChinaInstitute of Translational Medicine, Nanchang University, Nanchang 330031, ChinaInstitute of Translational Medicine, Nanchang University, Nanchang 330031, ChinaInstitute of Translational Medicine, Nanchang University, Nanchang 330031, ChinaInstitute of Translational Medicine, Nanchang University, Nanchang 330031, ChinaInstitute of Translational Medicine, Nanchang University, Nanchang 330031, ChinaInstitute of Translational Medicine, Nanchang University, Nanchang 330031, ChinaGeorgia Cancer Center, Augusta University, Augusta, GA 30912, USADepartment of Basic Medical Science, Shock/Trauma Research Center, School of Medicine, University of Missouri-Kansas City, Kansas City, MO 64108, USAInstitute of Translational Medicine, Nanchang University, Nanchang 330031, ChinaInstitute of Translational Medicine, Nanchang University, Nanchang 330031, ChinaCD38 was first identified as a lymphocyte-specific antigen and then has been found to be widely expressed in a variety of cell types. The functions of CD38 are involved in numerous biological processes including immune responses. Here, we showed the downregulations of both TLR2 mRNA and protein in macrophages from CD38−/− mice and in CD38 knockdown RAW264.7 cells. Several NF-κB-binding motifs in the promoter region of the TLR2 gene were identified by the bioinformatics analysis and were confirmed by the luciferase activity assay with the different truncated TLR2 promoters. CD38 deficiency resulted in the reduction of NF-κB p65 and acetyl-NF-κB p65 (Ac-p65) levels as determined by Western blot. The expression of Sirt1 did not change, but an increased activity of Sirt1 was observed in CD38-deficient macrophages. Inhibition of the Sirt1/NF-κB signaling pathway resulted in downregulation of TLR2 expression in RAW264.7 cells. However, re-expression of CD38 in the knockdown clones reversed the effect on Sirt1/NF-κB/TLR2 signaling, which is NAD-dependent. Moreover, the inflammatory cytokines including G-CSF, IL-1alpha, IL-6, MCP-1, MIP-1alpha, and RANTES were increased in CD38 knockdown RAW264.7 cells. Taken together, our data demonstrated that CD38 deficiency enhances inflammatory response in macrophages, and the mechanism may be partly associated with increased Sirt1 activity, which promoted NF-κB deacetylation and then inhibited expression of the TLR2 gene. Obviously, our study may provide an insight into the molecular mechanisms in CD38-mediated inflammation.http://dx.doi.org/10.1155/2018/8736949 |
| spellingShingle | Yisong Qian Chuqiao Chen Leliang Ma Ziwei Wang Ling-Fang Wang Li Zuo Yaqin Yang Xiang Huang Meixiu Jiang Xiaolei Wang Huidong Shi Mingui Fu Ke-Yu Deng Hong-Bo Xin CD38 Deficiency Promotes Inflammatory Response through Activating Sirt1/NF-κB-Mediated Inhibition of TLR2 Expression in Macrophages Mediators of Inflammation |
| title | CD38 Deficiency Promotes Inflammatory Response through Activating Sirt1/NF-κB-Mediated Inhibition of TLR2 Expression in Macrophages |
| title_full | CD38 Deficiency Promotes Inflammatory Response through Activating Sirt1/NF-κB-Mediated Inhibition of TLR2 Expression in Macrophages |
| title_fullStr | CD38 Deficiency Promotes Inflammatory Response through Activating Sirt1/NF-κB-Mediated Inhibition of TLR2 Expression in Macrophages |
| title_full_unstemmed | CD38 Deficiency Promotes Inflammatory Response through Activating Sirt1/NF-κB-Mediated Inhibition of TLR2 Expression in Macrophages |
| title_short | CD38 Deficiency Promotes Inflammatory Response through Activating Sirt1/NF-κB-Mediated Inhibition of TLR2 Expression in Macrophages |
| title_sort | cd38 deficiency promotes inflammatory response through activating sirt1 nf κb mediated inhibition of tlr2 expression in macrophages |
| url | http://dx.doi.org/10.1155/2018/8736949 |
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