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Papers of the Week

Papers: 23 Mar 2024 - 29 Mar 2024

2024 Mar 22

Biochem Pharmacol


Neutrophil-derived oxidative stress contributes to skin inflammation and scratching in a mouse model of allergic contact dermatitis via triggering pro-inflammatory cytokine and pruritogen production in skin.


Yang Y, Pan Y, Liu B, Zhang Y, Yin C, Wang J, Nie H, Xu R, Tai Y, He X, Shao X, Liang Y, Fang J, Liu B


Allergic contact dermatitis (ACD) is a common skin disease featured with skin inflammation and a mixed itch/pain sensation. The itch/pain causes the desire to scratch, affecting both physical and psychological aspects of patients. Nevertheless, the mechanisms underlying itch/pain sensation of ACD still remain elusive. Here, we found that oxidative stress and oxidation-related injury were remarkably increased in the inflamed skin of a mouse model of ACD. Reducing oxidative stress significantly attenuated itch/pain-related scratching, allokonesis and skin inflammation. RNA-Sequencing reveals oxidative stress contributes to a series of skin biological processes, including inflammation and immune response. Attenuating oxidative stress reduces overproduction of IL-1β and IL-33, two critical cytokines involved in inflammation and pain/itch, in the inflamed skin of model mice. Exogenously injecting HO into the neck skin of naïve mice triggered IL-33 overproduction in skin keratinocytes and induced scratching, which was reduced in mice deficient in IL-33 receptor ST2. ACD model mice showed remarkable neutrophil infiltration in the inflamed skin. Blocking neutrophil infiltration reduced oxidative stress and attenuated scratching and skin inflammation. Therefore, our study reveals a critical contribution of neutrophil-derived oxidative stress to skin inflammation and itch/pain-related scratching of ACD model mice via mechanisms involving the triggering of IL-33 overproduction in skin keratinocytes. Targeting skin oxidative stress may represent an effective therapy for ameliorating ACD.