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Background: Atopic dermatitis (AD) is a chronic inflammatory skin disease with immunopathologic features that vary depending on the duration of the lesion. Skin lesions of AD patients show an increased number of Th2 cells in the dermis and superficial Staphylococcus aureus colonization. The purpose of this study was to predict the effects of peptido- glycan (PEG) from S. aureus on the induction of interleukin (IL)-4 production in AD patients., Methods: PEG was applied to barrier-disrupted abdominal mouse skin every 5 days. Twenty days later, IL-4 production in the spleen was investigated by reverse transcription-polymerase chain reaction (RT-PCR). Spleen cells from normal mice were also treated in vitro with PEG and processed for IL-4 production by RT-PCR and enzyme-linked immunosorbent assay., Results: IL-4 production was significantly increased in the spleen of PEG-treated mice compared with that of PBS-applied mice. In addition, in vitro experiments demonstrated that PEG was able to induce IL-4 production in murine spleen cells. Furthermore, IL-4 production was associated with IL-18 production, but not with IL-2 production from PEG-stimulated spleen cells, and IL-4 mRNA was expressed in CD4+ lymphocytes in the spleen cells. In in vivo experiments, percutaneous treatment with PEG induced mRNA expression not only for IL-4 but also for IL-18 in the spleen., Conclusion: These results suggest that PEG may influence the induction of a Th2-dominant cytokine response in AD patients through IL-4 production from CD4+ T cells stimulated with PEG-induced IL-18., ((c) 2008 S. Karger AG, Basel)

Background: Previously, we found that percutaneous application of peptidoglycan (PEG) from Staphylococcus aureus increased the number of mast cells in the dermis, as seen in patients with atopic dermatitis. However, the origin of the mast cells infiltrating the dermis was not known. Our aim was to determine the origin of the skin mast cells induced by the percutaneous PEG application in mice., Methods: PEG was applied to barrier-disrupted abdominal skin of mice every 5 days. Twenty days after the first application, mast cells were detected in the spleen cells by alcian blue-safranin staining. Expression of mast cell proteases and cytokines in the skin or spleen was investigated by reverse transcription-polymerase chain reaction., Results: Percutaneous application of PEG increased the numbers of alcian blue-positive and safranin-negative mast cells in the spleen. Reverse transcription-polymerase chain reaction analysis of the spleen showed that these mast cells expressed mouse mast cell protease (MMCP)-1, MMCP-4, MMCP-5, and mast cell carboxypeptidase, suggesting that they were immature cells positioned developmentally between mucosal mast cells and connective tissue mast cells. In vitro long-term culture of spleen cells in the presence of PEG induced mast cell development. The features of these mast cells were coincident with those seen in the spleens of PEG-applied mice. Furthermore, when mice were intradermally injected, their skin showed increased levels of expression of mRNAs of MMCP-4, MMCP-5, and mast cell carboxypeptidase, but not MMCP-1. Similar mRNA expression was observed in the skin of PEG-applied mice., Conclusions: Percutaneous application of PEG may lead to the development of mast cells in the spleens of mice and contribute to an increase in mast cell numbers in the dermis, as seen in the skin lesions of atopic dermatitis patients., (Copyright (c) 2006 S. Karger AG, Basel.)