Heme oxygenase 1 attenuates the development of atopic dermatitis-like lesions in mice: Implications for human disease

作者：Kirino Mio; Kirino Yohei; Takeno Mitsuhiro; Nagashima Yoji; Takahashi Kazuo; Kobayashi Masayoshi; Murakami Shuji; Hirasawa Tsutomu; Ueda Atsuhisa; Aihara Michiko; Ikezawa Zenro; Ishigatsubo Yoshiaki^*

来源：Journal of Allergy and Clinical Immunology, 2008, 122(2): 290-297.

DOI：10.1016/j.jaci.2008.05.031

• atopic dermatitis
• heme oxygenase 1
• allergy
• inflammation

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 140-1 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.

• 出版日期2008-8