Downregulation of PU.1 leads to decreased expression of Dectin-1 in alveolar macrophages during Pneumocystis pneumonia

Chen Zhang; Shao-Hung Wang; Chung-Ping Liao; Shoujin Shao; Mark E Lasbury; Pamela J Durant; Chao-Hung Lee

doi:10.1128/IAI.01141-09

Downregulation of PU.1 leads to decreased expression of Dectin-1 in alveolar macrophages during Pneumocystis pneumonia

Chen Zhang, Shao-Hung Wang, Chung-Ping Liao, Shoujin Shao, Mark E Lasbury, Pamela J Durant, Chao-Hung Lee

Graduate Institute of Medical Sciences

Research output: Contribution to journal › Article › peer-review

19 Citations (Scopus)

Abstract

Dectin-1 is an important macrophage phagocytic receptor recognizing fungal beta-glucans. In this study, the mRNA levels of the Dectin-1 gene were found to be decreased by 61% in alveolar macrophages (AMs) from Pneumocystis-infected mice. The expression of Dectin-1 protein on the surface of these cells was also significantly decreased. By fluorescence in situ hybridization, mRNA expression levels of the transcription factor PU.1 were also found to be significantly reduced in AMs from Pneumocystis-infected mice. Electrophoretic mobility shift assay showed that PU.1 protein bound Dectin-1 gene promoter. With a luciferase reporter gene driven by the Dectin-1 gene promoter, the expression of the PU.1 gene in NIH 3T3 cells was found to enhance the luciferase activity in a dose-dependent manner. PU.1 expression knockdown by small interfering RNA (siRNA) caused a 63% decrease in Dectin-1 mRNA level and 40% decrease in protein level in AMs. Results of this study indicate that downregulation of PU.1 during Pneumocystis pneumonia leads to decreased expression of Dectin-1 in AMs.

Original language	English
Pages (from-to)	1058-65
Number of pages	8
Journal	Infection and Immunity
Volume	78
Issue number	3
DOIs	https://doi.org/10.1128/IAI.01141-09
Publication status	Published - Mar 2010

Keywords

3T3 Cells
Animals
Artificial Gene Fusion
DNA/metabolism
Down-Regulation
Electrophoretic Mobility Shift Assay
Female
Gene Expression Profiling
Genes, Reporter
Lectins, C-Type
Luciferases/biosynthesis
Macrophages, Alveolar/chemistry
Membrane Proteins/analysis
Mice
Nerve Tissue Proteins/biosynthesis
Pneumocystis/immunology
Pneumonia, Pneumocystis/immunology
Promoter Regions, Genetic
Protein Binding
Proto-Oncogene Proteins/antagonists & inhibitors
Trans-Activators/antagonists & inhibitors

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10.1128/IAI.01141-09

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title = "Downregulation of PU.1 leads to decreased expression of Dectin-1 in alveolar macrophages during Pneumocystis pneumonia",

abstract = "Dectin-1 is an important macrophage phagocytic receptor recognizing fungal beta-glucans. In this study, the mRNA levels of the Dectin-1 gene were found to be decreased by 61% in alveolar macrophages (AMs) from Pneumocystis-infected mice. The expression of Dectin-1 protein on the surface of these cells was also significantly decreased. By fluorescence in situ hybridization, mRNA expression levels of the transcription factor PU.1 were also found to be significantly reduced in AMs from Pneumocystis-infected mice. Electrophoretic mobility shift assay showed that PU.1 protein bound Dectin-1 gene promoter. With a luciferase reporter gene driven by the Dectin-1 gene promoter, the expression of the PU.1 gene in NIH 3T3 cells was found to enhance the luciferase activity in a dose-dependent manner. PU.1 expression knockdown by small interfering RNA (siRNA) caused a 63% decrease in Dectin-1 mRNA level and 40% decrease in protein level in AMs. Results of this study indicate that downregulation of PU.1 during Pneumocystis pneumonia leads to decreased expression of Dectin-1 in AMs.",

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author = "Chen Zhang and Shao-Hung Wang and Chung-Ping Liao and Shoujin Shao and Lasbury, {Mark E} and Durant, {Pamela J} and Chao-Hung Lee",

year = "2010",

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doi = "10.1128/IAI.01141-09",

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publisher = "American Society for Microbiology",

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AU - Zhang, Chen

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AU - Liao, Chung-Ping

AU - Shao, Shoujin

AU - Lasbury, Mark E

AU - Durant, Pamela J

AU - Lee, Chao-Hung

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N2 - Dectin-1 is an important macrophage phagocytic receptor recognizing fungal beta-glucans. In this study, the mRNA levels of the Dectin-1 gene were found to be decreased by 61% in alveolar macrophages (AMs) from Pneumocystis-infected mice. The expression of Dectin-1 protein on the surface of these cells was also significantly decreased. By fluorescence in situ hybridization, mRNA expression levels of the transcription factor PU.1 were also found to be significantly reduced in AMs from Pneumocystis-infected mice. Electrophoretic mobility shift assay showed that PU.1 protein bound Dectin-1 gene promoter. With a luciferase reporter gene driven by the Dectin-1 gene promoter, the expression of the PU.1 gene in NIH 3T3 cells was found to enhance the luciferase activity in a dose-dependent manner. PU.1 expression knockdown by small interfering RNA (siRNA) caused a 63% decrease in Dectin-1 mRNA level and 40% decrease in protein level in AMs. Results of this study indicate that downregulation of PU.1 during Pneumocystis pneumonia leads to decreased expression of Dectin-1 in AMs.

AB - Dectin-1 is an important macrophage phagocytic receptor recognizing fungal beta-glucans. In this study, the mRNA levels of the Dectin-1 gene were found to be decreased by 61% in alveolar macrophages (AMs) from Pneumocystis-infected mice. The expression of Dectin-1 protein on the surface of these cells was also significantly decreased. By fluorescence in situ hybridization, mRNA expression levels of the transcription factor PU.1 were also found to be significantly reduced in AMs from Pneumocystis-infected mice. Electrophoretic mobility shift assay showed that PU.1 protein bound Dectin-1 gene promoter. With a luciferase reporter gene driven by the Dectin-1 gene promoter, the expression of the PU.1 gene in NIH 3T3 cells was found to enhance the luciferase activity in a dose-dependent manner. PU.1 expression knockdown by small interfering RNA (siRNA) caused a 63% decrease in Dectin-1 mRNA level and 40% decrease in protein level in AMs. Results of this study indicate that downregulation of PU.1 during Pneumocystis pneumonia leads to decreased expression of Dectin-1 in AMs.

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KW - Lectins, C-Type

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KW - Protein Binding

KW - Proto-Oncogene Proteins/antagonists & inhibitors

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DO - 10.1128/IAI.01141-09

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SP - 1058

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JO - Infection and Immunity

JF - Infection and Immunity

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ER -

Downregulation of PU.1 leads to decreased expression of Dectin-1 in alveolar macrophages during Pneumocystis pneumonia

Abstract

Keywords

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