1. ¹Unit of Excellence in Immunotoxicology, Finnish Institute of Occupational Health, Helsinki, Finland
2. ²Department of Dermatology and Venereology, Qingdao University Medical College Hospital, PR China
3. ³Mammalian Genetics Section, National Institutes of Health, Maryland, USA
4. ⁴Team for Biological Mechanisms and Prevention of Work-related Diseases, Finnish Institute of Occupational Health, Helsinki, Finland
5. ⁵Department of Pathology, Helsinki University Central Hospital, Finland
6. ⁶Department of Pathology, Kymenlaakso Central Hospital, Finland
7. ⁷Control of Hypersensitivity Diseases, Finnish Institute of Occupational Health, Helsinki, Finland

Correspondence: Dr Harri T. Alenius, Finnish Institute of Occupational Health, Topeliuksenkatu 41 a A, FIN-00250 Helsinki, Finland. E-mail: Harri.Alenius@ttl.fi

Received 22 August 2006; Revised 1 December 2006; Accepted 20 January 2007; Published online 12 April 2007.

Abstract

Atopic dermatitis (AD) is a common chronic inflammatory skin disease characterized by itchy, dry, and inflamed skin. Transforming growth factor (TGF)- is an important fibrogenic and immunomodulatory factor that regulates cellular processes in the injured and inflamed skin. This study examines the role of the TGF-–Smad signaling pathway using Smad3-deficient mice in a murine model of AD. Dermatitis was induced in mice by epicutaneous application of ovalbumin (OVA) applied in a patch to tape-stripped skin. OVA-specific IgE and IgG_2a antibody levels were measured by ELISA. Skin biopsies from sensitized skin areas were used for RNA isolation, histology, and immunohistochemical examination. The thickness of dermis was significantly reduced in OVA-sensitized skin of Smad3^-/- mice. The defect in the dermal thickness was accompanied by a decrease in the expression of mRNA for proinflammatory cytokines IL-6 and IL-1 in the OVA-sensitized skin. In contrast, the number of mast cells was significantly increased in OVA-sensitized skin of Smad3^-/- mice, which also exhibited elevated levels of OVA-specific IgE. These results demonstrate that the Smad3-pathway regulates allergen-induced skin inflammation and systemic IgE antibody production in a murine model AD. The Smad3 signaling pathway might be a potential target in the therapy of allergic skin diseases.