Abstract
Redox-regulating molecule, recombinant human thioredoxin (rhTRX) which shows anti-inflammatory, and anti-oxidative effects against lipopolysaccharide (LPS)-stimulated inflammation and regulate protein expression levels. LPS-induced reactive oxygen intermediates (ROI) and NO production were inhibited by exogenous rhTRX. We identified up/downregulated intracellular proteins under the LPS-treated condition in exogenous rhTRX-treated A375 cells compared with non-LPS-treated cells via 2-DE proteomic analysis. Also, we quantitatively measured cytokines of in vivo mouse inflammation models using cytometry bead array. Exogenous rhTRX inhibited LPS-stimulated production of ROI and NO levels. TIP47 and ATP synthase may influence the inflammation-related lipid accumulation by affecting lipid metabolism. The modulation of skin redox environments during inflammation is most likely to prevent alterations in lipid metabolism through upregulation of TIP47 and ATP synthase and downregulation of inflammatory cytokines. Our results demonstrate that exogenous rhTRX has anti-inflammatory properties and intracellular regulatory activity in vivo and in vitro. Monitoring of LPS-stimulated pro-inflammatory conditions treated with rhTRX in A375 cells could be useful for diagnosis and follow-up of inflammation reduction related with candidate proteins. These results have a therapeutic role in skin inflammation therapy.
Highlights
Skin, the largest organ of the human body, is the most important interface between the environment and the body
In cells treated with recombinant human thioredoxin (rhTRX), the increased intracellular reactive oxygen intermediates (ROI) level following LPS stimulation decreased, which indicates that exogenous rhTRX treatment diminished the oxidative stress
It has been reported that extracellular levels of TRX increase in response to oxidative stress and inflammation,8,19 which indicates the direct involvement of TRX in cellular defense systems
Summary
The largest organ of the human body, is the most important interface between the environment and the body. It is constantly exposed to chemical and physical environmental pollutants or their metabolic toxicants, which are associated with a wide range of inflammatory skin diseases. Inflammatory skin diseases, such as dermatitis, systemic inflammatory response syndrome (SIRS) and sepsis, are known to affect the whole body, which results in systemic inflammation, organ dysfunction and organ failure.. Severe depletion of antioxidants in the skin caused by prolonged exposure to reactive oxygen species (ROS) results in insufficient protection, triggering cellular damage.. Reactive oxygen intermediates (ROI) have emerged as promising targets for anti-inflammatory drug discovery. Topical application or oral administration of antioxidants has been suggested as an effective preventive therapy for inflammatory skin diseases
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