S Shibama1,2, T Ugajin1, T Yamaguchi3, H Yokozeki1. 1. Department of Dermatology, Graduate School, Tokyo Medical and Dental University, Tokyo, Japan. 2. Department of Dermatology, Sakura Hospital, Medical Center, Toho University, Sakura City, Japan. 3. Department of Biochemical Genetics, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, Japan.
Abstract
BACKGROUND: Bilirubin is an essential antioxidant. Its oxidative metabolites, biopyrrins, are sensitive urinary markers of oxidative stress. Multiple studies suggest that oxidative stress affects the pathogenesis of skin diseases such as atopic dermatitis (AD). AIM: To examine oxidative stress-induced bilirubin oxidation and its association with AD pathogenesis in adults. METHODS: In total, 11 patients with AD and 7 healthy controls (HCs) were enrolled. Bilirubin oxidation profiles in the combined urine of the patients and that of the HCs were examined using high-performance liquid chromatography (HPLC) and fast atom bombardment mass spectrometry. The concentrations of urinary biopyrrins and serum biomarkers for AD disease severity, such as IgE and thymus and activation-regulated chemokine (TARC)/CCL17, were measured by ELISA to determine correlations between urinary biopyrrins and serum biomarkers. Local bilirubin oxidation in AD skin lesions was assessed by immunohistochemical analyses using two antibodies against bilirubin. RESULTS: Levels of dipyrrole-monopyrrole-aldehyde, a novel urinary biopyrrin, were higher in patients with AD than in HCs, and increased with disease severity based on the SCORing Atopic Dermatitis (SCORAD) objective scoring system. Additionally, urinary biopyrrin levels correlated significantly with serum IgE and TARC/CCL17 levels. Furthermore, immunohistochemical analyses revealed that biopyrrins were strongly expressed in both infiltrating and resident cells in AD lesions. However, bilirubin was expressed at low levels in the lesions, suggesting that bilirubin oxidation is augmented in AD lesions. CONCLUSIONS: Bilirubin oxidation derived from oxidative stress in the skin lesions can be associated with disease severity of AD.
BACKGROUND:Bilirubin is an essential antioxidant. Its oxidative metabolites, biopyrrins, are sensitive urinary markers of oxidative stress. Multiple studies suggest that oxidative stress affects the pathogenesis of skin diseases such as atopic dermatitis (AD). AIM: To examine oxidative stress-induced bilirubin oxidation and its association with AD pathogenesis in adults. METHODS: In total, 11 patients with AD and 7 healthy controls (HCs) were enrolled. Bilirubin oxidation profiles in the combined urine of the patients and that of the HCs were examined using high-performance liquid chromatography (HPLC) and fast atom bombardment mass spectrometry. The concentrations of urinary biopyrrins and serum biomarkers for AD disease severity, such as IgE and thymus and activation-regulated chemokine (TARC)/CCL17, were measured by ELISA to determine correlations between urinary biopyrrins and serum biomarkers. Local bilirubin oxidation in AD skin lesions was assessed by immunohistochemical analyses using two antibodies against bilirubin. RESULTS: Levels of dipyrrole-monopyrrole-aldehyde, a novel urinary biopyrrin, were higher in patients with AD than in HCs, and increased with disease severity based on the SCORing Atopic Dermatitis (SCORAD) objective scoring system. Additionally, urinary biopyrrin levels correlated significantly with serum IgE and TARC/CCL17 levels. Furthermore, immunohistochemical analyses revealed that biopyrrins were strongly expressed in both infiltrating and resident cells in AD lesions. However, bilirubin was expressed at low levels in the lesions, suggesting that bilirubin oxidation is augmented in AD lesions. CONCLUSIONS:Bilirubin oxidation derived from oxidative stress in the skin lesions can be associated with disease severity of AD.