Percutaneous application of peptidoglycan from Staphylococcus aureus induces an increase in mast cell numbers in the dermis of mice

Abstract

Atopic dermatitis (AD) is a chronic inflammatory skin disease with immunopathologic features that vary depending on the duration of the lesion. The dermis of lesional skin of AD patients shows an increased number of inflammatory cells such as mast cells, eosinophils and mononuclear cells and superficial Staphylococcus aureus colonization. The purpose of this study was to determine the effects of peptidoglycan (PEG) from S. aureus on mast cell induction in murine skin. PEG was applied to barrier-disrupted abdominal skin of mice every 5 days and the number of mast cells in the abdominal skin was counted 20 days after the first application. The cytokine response was investigated by RT-PCR and immunohistologic analysis. The number of mast cells in the skin of mice treated with PEG was increased significantly compared with that of mice given phosphate-buffered saline. In addition, application of PEG to the abdominal skin increased the expression of mRNA for transforming growth factor-beta(1) (TGF-beta(1)), which supports mast cell migration, but not that for IL-3 or stem cell factor, which support both mast cell proliferation and mast cell migration. Immunohistologic analysis demonstrated that levels of TGF-beta(1) transcripts corresponded with those of protein synthesis in the epidermis. TGF-beta(1) was found to be highly expressed in keratinocytes of the basal epidermis of PEG-treated skin. Furthermore, intraperitoneal injection of anti-TGF-beta(1) antibodies neutralized the induction of mast cells into the skin. These results suggest that PEG may have the ability to induce an increase in mast cell numbers in the skin through TGF-beta(1) production by epidermal keratinocytes. Skin inflammation might therefore be linked to colonization with S. aureus in AD patients.