Research Papers:

IRF5 is elevated in childhood-onset SLE and regulated by histone acetyltransferase and histone deacetylase inhibitors

Jin Shu, Ling Li, Lan-Bo Zhou, Jun Qian, Zhi-Dan Fan, Li-Li Zhuang, Lu-Lu Wang, Rui Jin, Hai-Guo Yu and Guo-Ping Zhou _

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Oncotarget. 2017; 8:47184-47194. https://doi.org/10.18632/oncotarget.17586

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Jin Shu1,*, Ling Li1,*, Lan-Bo Zhou2, Jun Qian1, Zhi-Dan Fan3, Li-Li Zhuang4, Lu-Lu Wang4, Rui Jin4, Hai-Guo Yu3 and Guo-Ping Zhou4

1Wuxi People’s Hospital Affiliated to Nanjing Medical University, Wuxi 214023, P.R. China

2The First Clinical Medical School, Nanjing Medical University, Nanjing 210029, P.R. China

3Nanjing Children′s Hospital, Nanjing Medical University, Nanjing 210029, P.R. China

4The First Affiliated Hospital, Nanjing Medical University, Nanjing 210029, P.R. China

*These authors contributed equally to this work

Correspondence to:

Guo-Ping Zhou, email: gpzhou2013@126.com

Hai-Guo Yu, email: yuhaiguo73@126.com

Keywords: IRF5, systemic lupus erythematosus, HDAC inhibitors, Trichostatin A, p300

Received: September 28, 2016     Accepted: April 17, 2017     Published: May 03, 2017


Interferon regulatory factor 5 (IRF5) plays a critical role in the induction of type I interferon, proinflammatory cytokines and chemokines, and participates in the pathogenesis of autoimmune diseases such as systemic lupus erythematosus (SLE). However, the relationship between IRF5 and childhood-onset SLE remains elusive. In the present study, we demonstrated that levels of mRNA expression of IRF5, IFN-α, and Sp1 were significantly increased in childhood-onset SLE, as seen on quantitative real-time PCR, and the expression of Sp1 and IFN-α was positively correlated with IRF5. In addition to being used as antitumor drugs, a number of histone deacetylase inhibitors (HDACi) display potent anti-inflammatory properties; however, their effects on IRF5 expression remain unclear. In this study, we identified that HDACi trichostatin A (TSA) and histone acetyltransferase (HAT)-p300 downregulated IRF5 promoter activity, mRNA expression, and protein level, whereas the HAT-p300/CBP-associated factor had no effect. Moreover, TSA inhibited the production of TNF-α and IL-6 in differentiated THP-1cells. Furthermore, chromatin immunoprecipitation assays revealed that TSA inhibited DNA binding of Sp1, RNA polymerase II, HDAC3, and p300 to the core promoter region of IRF5. Our results suggest that HDACi may have therapeutic potential in patients with autoimmune diseases such as SLE through repression of IRF5 expression.

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