Inhibition of early T cell cytokine production by arsenic trioxide occurs independently of Nrf2

• DOI: 10.1371/journal.pone.0185579
• Publication Date: 2017-10-19T17:32:29Z
• Authors: Kelly R. VanDenBerg; Robert A. Freeborn; Sheng Liu; Rebekah C. Kennedy; Joseph W. Zagorski; Cheryl E. Rockwell
• Keywords: Splenocyte; KEAP1; Arsenic Trioxide

Nuclear factor erythroid 2-related 2 (Nrf2) is a stress-activated transcription that induces variety of cytoprotective genes. Nrf2 also mediates immunosuppressive effects in multiple inflammatory models. Upon activation, dissociates from its repressor protein, Keap1, and translocates to the nucleus where it target The Nrf2-Keap1 interaction disrupted by environmental toxicant chemotherapeutic agent arsenic trioxide (ATO). purpose present study was determine ATO on early events T cell activation role those effects. genes Hmox-1, Nqo-1, Gclc were all upregulated (1–2 μM) splenocytes derived wild-type, but not Nrf2-null, mice, suggesting activated splenocytes. inhibited IFNγ, IL-2, GM-CSF mRNA protein production wild-type with activator, anti-CD3/anti-CD28. However, decreased these cytokines Nrf2-null inhibition independent Nrf2. Interestingly, TNFα secretion, expression, due post-transcriptional modification. In addition, c-Fos DNA binding significantly diminished anti-CD3/anti-CD28, consistent observed cytokine ATO. Collectively, this suggests although activates splenocytes, occurs independently may instead be impaired AP-1 binding.