BACKGROUND: Oxidative stress has been implicated in the exacerbation of atopic dermatitis (AD). OBJECTIVE: We sought to investigate the pathophysiologic roles of inducible antioxidant heme oxygenase (HO) 1 in the development of AD. METHODS: Serum HO-1 levels of patients with AD (n = 100) and age-matched healthy control subjects (n = 72) were determined by means of ELISA. The relationships between serum HO-1 levels and clinical severities, laboratory parameters, and cytokines/chemokines were assessed. Skin lesions of patients with AD and psoriasis were analyzed by means of immunohistochemistry. A murine AD model, DS-Nh, was used to further investigate localization and function of HO-1. Evaluation of symptoms, serum IgE and IL-18 levels, immunoblotting results, and histologic analyses of skin were performed. The effect of intraperitoneally administered hemin, a potent HO-1 inducer, or zinc protoporphyrin IX, an inhibitor of HO, was monitored. RESULTS: Serum HO-1 levels were significantly increased in patients with AD compared with those seen in healthy control subjects and were associated with AD disease severity. Serum HO-1 levels correlated with serum IgE, lactate dehydrogenase, IL-18, and thymus and activation-regulated chemokine levels. HO-1-expressing cells were accumulated in skin lesions of patients with AD and DS-Nh mice. Immunofluorescence of mouse skin lesions revealed that HO-1-positive cells were macrophages and dendritic cells. Treatment with hemin, but not with zinc protoporphyrin IX, attenuated the development of the skin lesions in DS-Nh mice and reduced serum IL-18 levels. CONCLUSION: HO-1 levels were increased in sera and skin lesions of patients with AD. Enhancement of HO-1 attenuated the development of skin lesions in mice, suggesting that HO-1 induction offers a promising therapeutic strategy for AD.
BACKGROUND: Oxidative stress has been implicated in the exacerbation of atopic dermatitis (AD). OBJECTIVE: We sought to investigate the pathophysiologic roles of inducible antioxidant heme oxygenase (HO) 1 in the development of AD. METHODS: Serum HO-1 levels of patients with AD (n = 100) and age-matched healthy control subjects (n = 72) were determined by means of ELISA. The relationships between serum HO-1 levels and clinical severities, laboratory parameters, and cytokines/chemokines were assessed. Skin lesions of patients with AD and psoriasis were analyzed by means of immunohistochemistry. A murineAD model, DS-Nh, was used to further investigate localization and function of HO-1. Evaluation of symptoms, serum IgE and IL-18 levels, immunoblotting results, and histologic analyses of skin were performed. The effect of intraperitoneally administered hemin, a potent HO-1 inducer, or zinc protoporphyrin IX, an inhibitor of HO, was monitored. RESULTS: Serum HO-1 levels were significantly increased in patients with AD compared with those seen in healthy control subjects and were associated with AD disease severity. Serum HO-1 levels correlated with serum IgE, lactate dehydrogenase, IL-18, and thymus and activation-regulated chemokine levels. HO-1-expressing cells were accumulated in skin lesions of patients with AD and DS-Nh mice. Immunofluorescence of mouse skin lesions revealed that HO-1-positive cells were macrophages and dendritic cells. Treatment with hemin, but not with zinc protoporphyrin IX, attenuated the development of the skin lesions in DS-Nh mice and reduced serum IL-18 levels. CONCLUSION: HO-1 levels were increased in sera and skin lesions of patients with AD. Enhancement of HO-1 attenuated the development of skin lesions in mice, suggesting that HO-1 induction offers a promising therapeutic strategy for AD.
Authors: Yasser E Elassiuty; Jared Klarquist; Jodi Speiser; Randa M Yousef; Abdelaziz A El Refaee; Nahla S Hunter; Olfat G Shaker; Mohan Gundeti; Ludmila Nieuweboer-Krobotova; I Caroline Le Poole Journal: Exp Dermatol Date: 2011-03-22 Impact factor: 3.960
Authors: Adam J Case; Joshua M Madsen; David G Motto; David K Meyerholz; Frederick E Domann Journal: Free Radic Biol Med Date: 2012-12-05 Impact factor: 7.376