Nrf2 Involvement in Chemical-Induced Skin Innate Immunity

Abstract

Exposure to certain chemicals disturbs skin homeostasis. In particular, protein-reactive chemical contact sensitizers trigger an inflammatory immune response resulting in eczema and allergic contact dermatitis. Chemical sensitizers activate innate immune cells which orchestrate the skin immune response. This involves oxidative and inflammatory pathways. In parallel, the Nrf2/Keap1 pathway, a major ubiquitous regulator of cellular oxidative and electrophilic stress is activated in the different skin innate immune cells including epidermal Langerhans cells and dermal dendritic cells, but also in keratinocytes. In this context, Nrf2 shows a strong protective capacity through the downregulation of both the oxidative stress and inflammatory pathways. In this review we highlight the important role of Nrf2 in the control of the innate immune response of the skin to chemical sensitizers.

Topical Application of Phlorotannins from Brown Seaweed Mitigates Radiation Dermatitis in a Mouse Model

“…Recent studies have demonstrated that the NRF2 pathway is implicated in both inflammatory and oxidative stress responses [ 36 ], and its modulation may be effective for managing inflammatory diseases, including dermatitis [ 37 , 38 , 39 ]. Several chemicals that can stimulate NRF2 expression have been tested for their application as therapeutic agents for RD [ 40 ].…”

“…These data suggest that PTNs effectively suppress or delay the acute inflammatory response in the early phase of RD. Crosstalk occurs between the NRF2 and NF-κB pathways: NRF2 signaling inhibits the NF-κB pathway and vice versa [ 36 , 37 ]. Thus, PTNs may suppress the radiation-induced NF-κB pathway via NRF2 activation, thereby reducing the RD scores.…”

Antioxidant Defence Systems and Oxidative Stress in Poultry Biology: An Update

“…In normal physiological conditions, Nrf2 exists as an inactive complex with the negative regulator called Kelch-like-ECH-associated protein 1 (Keap1): a 624 amino acid, cysteine-rich, homodimeric zinc-finger protein [195]. In fact, Keap1 is responsible for forwarding Nrf2 to a Cul3-based E3 ligase with the following rapid 26S proteasome degradation with a half-life under physiological conditions of only ∼20 min [196,197]. Importantly, more than 27 cysteine residues possessing different reactivity and having various functional impact on Nrf2 were identified in Keap1.…”

“…Table 3. Principal functions of enzymes encoded by Nrf2 target genes and involved in the antioxidant defence [186,197,[202][203][204].…”

“…Importantly, Nrf2 was shown to restrict/prevent iron-or heme-mediated oxidative stress by affecting the expression of the FPN1, ferritin and HO-1 genes [250]. Regulation of the aforementioned antioxidants, NADPH-synthesizing enzymes, as well as others stress-response proteins are clearly shown to provide protection against oxidative and inflammatory damages [197,203,204,251]. Accumulating evidence clearly shows that Nrf2 can also regulate many important biological processes, including cell proliferation and differentiation, inflammation, autophagy, apoptosis, mitochondrial function or biogenesis as well as several metabolic pathways involved in iron/heme, glucose, glutamine, lipid, NADPH and pentose phosphate metabolism (for review and references, see Reference [198]).…”