CD38 deficiency promotes inflammatory response through activating sirt1/NF-κB-mediated inhibition of TLR2 expression in macrophages

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

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Article number8736949
JournalMediators of Inflammation
Volume2018
DOIs
StatePublished - Jan 1 2018

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Macrophages
Down-Regulation
Chemokine CCL3
Biological Phenomena
Chemokine CCL5
Granulocyte Colony-Stimulating Factor
Computational Biology
Luciferases
Genetic Promoter Regions
NAD
Interleukin-6
Clone Cells
Western Blotting
Lymphocytes
Cytokines
Inflammation
Gene Expression
Antigens
Messenger RNA
Genes

ASJC Scopus subject areas

  • Immunology
  • Cell Biology

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CD38 deficiency promotes inflammatory response through activating sirt1/NF-κB-mediated inhibition of TLR2 expression in macrophages. / Qian, Yisong; Chen, Chuqiao; Ma, Leliang; Wang, Ziwei; Wang, Ling Fang; Zuo, Li; Yang, Yaqin; Huang, Xiang; Jiang, Meixiu; Wang, Xiaolei; Shi, Huidong; Fu, Mingui; Deng, Ke Yu; Xin, Hong Bo.

In: Mediators of Inflammation, Vol. 2018, 8736949, 01.01.2018.

Research output: Contribution to journalArticle

Qian, Y, Chen, C, Ma, L, Wang, Z, Wang, LF, Zuo, L, Yang, Y, Huang, X, Jiang, M, Wang, X, Shi, H, Fu, M, Deng, KY & Xin, HB 2018, 'CD38 deficiency promotes inflammatory response through activating sirt1/NF-κB-mediated inhibition of TLR2 expression in macrophages', Mediators of Inflammation, vol. 2018, 8736949. https://doi.org/10.1155/2018/8736949
Qian, Yisong ; Chen, Chuqiao ; Ma, Leliang ; Wang, Ziwei ; Wang, Ling Fang ; Zuo, Li ; Yang, Yaqin ; Huang, Xiang ; Jiang, Meixiu ; Wang, Xiaolei ; Shi, Huidong ; Fu, Mingui ; Deng, Ke Yu ; Xin, Hong Bo. / CD38 deficiency promotes inflammatory response through activating sirt1/NF-κB-mediated inhibition of TLR2 expression in macrophages. In: Mediators of Inflammation. 2018 ; Vol. 2018.
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abstract = "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.",
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AU - Qian, Yisong

AU - Chen, Chuqiao

AU - Ma, Leliang

AU - Wang, Ziwei

AU - Wang, Ling Fang

AU - Zuo, Li

AU - Yang, Yaqin

AU - Huang, Xiang

AU - Jiang, Meixiu

AU - Wang, Xiaolei

AU - Shi, Huidong

AU - Fu, Mingui

AU - Deng, Ke Yu

AU - Xin, Hong Bo

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N2 - 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.

AB - 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.

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