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Inhibition of PARP1 Increases IRF-dependent Gene Transcription in Jurkat Cells

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Summary

Poly(ADP-ribose) polymerase 1 (PARP1) plays important roles in the regulation of transcription factors. Mounting evidence has shown that inhibition of PARP1 influences the expression of genes associated with inflammatory response. Interferon regulatory factor 1 (IRF1) is a critical transcription factor for the development of both the innate and adaptive immune responses against infections. However, the molecular mechanism through which PARP1 mediates the effects has not been clearly demonstrated. Jurkat cells were exposed to dexamethasone (Dex) or PARP1 inhibitor PJ34. The expression levels of IL-12, LMP2, OAS1 and PKR were detected using real-time RT-PCR. The interactions between PARP1 and IRF1 were examined by co-immunoprecipitation (co-IP) assays. We further explored the mechanism of PARP1 suppressing IRF1 by assessing the activities of interferon stimulated response element (ISRE). The mRNA expression of IL-12, LMP2, OAS1 and PKR was obviously suppressed by Dex in Jurkat cells, which could be rescued by PJ34 treatment. Luciferase study revealed that poly(ADP-ribosyl)- ation suppressed IRF1-mediated transcription through preventing the binding of IRF1 to ISREs. PARP1 inhibited IRF1-mediated transcription in Jurkat cells by preventing IRF1 binding to ISREs in the promoters of target genes. It is suggested that PARP1 is a crucial regulator of IRF1-mediated immune response. This study provides experimental evidence for the possible application of PARP1 inhibitors in the treatment of IRF1-related immune anergy.

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Authors and Affiliations

  1. Clinic Center of Human Gene Research, Union Hospital, Tongji Medical College, Huazhong, University of Science and Technology, Wuhan, 430022, China

    Cheng Wang, Meng Du, Dan Huang, Kun Huang & Kai Huang

  2. Institution of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China

    Cheng Wang, Meng Du, Dan Huang, Kun Huang & Kai Huang

Authors
  1. Cheng Wang
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  2. Meng Du
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  3. Dan Huang
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  4. Kun Huang
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  5. Kai Huang
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Correspondence to Kun Huang or Kai Huang.

Additional information

This work was supported by the National Natural Science Foundation of China (No. 81370263 and No. 81500348).

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Wang, C., Du, M., Huang, D. et al. Inhibition of PARP1 Increases IRF-dependent Gene Transcription in Jurkat Cells. CURR MED SCI 39, 356–362 (2019). https://doi.org/10.1007/s11596-019-2043-1

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  • DOI: https://doi.org/10.1007/s11596-019-2043-1

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