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

Research output: Contribution to journalArticlepeer-review

17 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 languageEnglish
Pages (from-to)1058-65
Number of pages8
JournalInfection and Immunity
Volume78
Issue number3
DOIs
Publication statusPublished - 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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