The role of Nrf2 in autoimmunity and infectious disease: Therapeutic possibilities

Persistent oxidative stress and inflammasome activation in CD14highCD16-monocytes from COVID-19 patients

“…Oxidative stress has been suggested to be a critical host factor in driving immune response exacerbation in several infectious diseases (Amaral et al, 2021; Erlich et al, 2020; Favier et al, 1994; Freeborn and Rockwell, 2021; Pohanka, 2013). However, the induction of inflammatory oxidative stress responses in circulating monocytes obtained from COVID-19 patients has not been formally investigated.…”

“…Several stress-related cellular processes have been reported to induce NLRP3 activation in response to distinct PAMPs and DAMPs, such as K + efflux (Munoz-Planillo et al, 2013), lysosomal disruption (Hornung et al, 2008), mitochondrial damage (Iyer et al, 2013; Zhou et al, 2011) and the generation of reactive oxygen species (ROS) (Martinon, 2010; Tschopp and Schroder, 2010). Since robust redox responses observed in hypoxic conditions during other pulmonary infections are commonly associated with exacerbated cytokine production and disease progression (Amaral et al, 2021; Erlich et al, 2020; Favier et al, 1994; Freeborn and Rockwell, 2021; Pohanka, 2013; Prabhakar et al, 2020), host oxidative stress has also been implicated in the pathogenesis of COVID-19 (Delgado-Roche and Mesta, 2020; Fakhri et al, 2020; Ntyonga-Pono, 2020).…”

Perfluorinated Carboxylic Acids with Increasing Carbon Chain Lengths Upregulate Amino Acid Transporters and Modulate Compensatory Response of Xenobiotic Transporters in HepaRG Cells

“…Indeed, it has been reported that oxidative stress and inflammation may contribute to PFOA-induced hepatotoxicity in mice (Yang et al, 2014). In addition, PNFA has been shown to produce immunotoxicity and have persistent effects on the immune system (Rockwell et al, 2013;Rockwell et al, 2017), whereas Nrf2 is known to have an important immunomodulatory effect (Freeborn and Rockwell, 2021). Our study suggests that PFCAs may also activate Nrf2 to regulate the expression of transporters in human hepatocytes as a compensatory response.…”

The Complicated Role of Nuclear Factor Erythroid-Derived 2-Like 2 in Allergy and Asthma

“…We recently published a review focused on the role of Nrf2 in autoimmunity and infectious disease (Freeborn and Rockwell, 2021). In addition, others have reviewed the role of Nrf2 in inflammation and Nrf2/NFκB crosstalk (Li et al, 2008a;Wardyn et al, 2015;Ahmed et al, 2017;Mohan and Gupta, 2018;Staurengo-Ferrari et al, 2018;Saha et al, 2020;Bhandari et al, 2021;Freeborn and Rockwell, 2021). To complement these previous reviews, the purpose of the present paper is to review what is known about the role of Nrf2 in asthma and allergy.…”

“…While much is known about the mechanism by which Nrf2 protects against reactive toxicants and oxidative stress, the mechanism by which Nrf2 modulates immune cell function is not nearly as well understood. We recently published a review focused on the role of Nrf2 in autoimmunity and infectious disease (Freeborn and Rockwell, 2021). In addition, others have reviewed the role of Nrf2 in inflammation and Nrf2/NFκB crosstalk (Li et al, 2008a;Wardyn et al, 2015;Ahmed et al, 2017;Mohan and Gupta, 2018;Staurengo-Ferrari et al, 2018;Saha et al, 2020;Bhandari et al, 2021;Freeborn and Rockwell, 2021).…”