The Nrf2 activator tBHQ promotes OVA-Elicited Food Allergy in Mice

Abstract ID 24335 Poster Board 225 There has been a steady rise in the prevalence of food allergy for the past couple of decades for reasons that are not completely understood. While previous studies from our lab demonstrated that a food antioxidant present in many processed foods, tert-butylhydroquinone (tBHQ), promotes the development of allergy in mice, our current experiment focuses on the dose response of tBHQ in the mice chow. Mice were fed AIN-93G with 0.0014% tBHQ (standard), 0.0007% tBHQ (50% of the standard), and 0.00028% tBHQ (20% of the standard) or control diet. Mice were exposed to OVA once every week for 4 weeks during the sensitization phase. Sensitization to OVA was assessed by the rise in OVA-specific IgE. Upon oral challenge, mice were monitored for hypothermia shock response (HSR) and the degranulation of mast cells. Sensitization with OVA elicited a more robust OVA-specific IgE antibody response in mice on the tBHQ diet with high concentration. Likewise, in response to OVA challenge, a greater drop in rectal temperature was observed in the mice on the high concentration of tBHQ diet post-challenge compared to control animals. In addition, because tBHQ is a robust activator of the transcription factor Nrf2 in immune cells, we aimed to determine the role of Nrf2 in these tBHQ-mediated effects. Therefore, we performed a PCR array on splenocytes from SCID mice (immune-deficient mice) who received either wild-type CD4 T cells or Nrf2-knockout CD4 T cells and were sensitized to OVA. We found that the Th2-related genes were downregulated, but Tregs and Th1-related genes were upregulated in mice that received Nrf2-null CD4 T cells. Taken together, these data suggest that exposure to tBHQ through diet promotes OVA sensitization and exacerbates anaphylactic response to OVA challenge in a mouse model of food allergy. This effect is tBHQ dose-dependent and dependent on the transcription factor Nrf2.