Peptidoglycan from Staphylococcus aureus induces IL-4 production from murine spleen cells via an IL-18-dependent mechanism.
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.


CONCLUSIONS
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.
Matsui
Katsuhiko
K
Department of Immunobiology, Meiji Pharmaceutical University, Tokyo, Japan. kmatsui@my-pharm.ac.jp
Wirotesangthong
Mali
M
Nishikawa
Akemi
A
D000279:Administration, Cutaneous; D000818:Animals; D003876:Dermatitis, Atopic / Q000276:immunology* / Q000382:microbiology; D005260:Female; D020382:Interleukin-18 / Q000235:genetics / Q000276:immunology*; D015847:Interleukin-4 / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D010457:Peptidoglycan / Q000008:administration & dosage / Q000276:immunology*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013047:Specific Pathogen-Free Organisms; D013154:Spleen / Q000276:immunology*; D013211:Staphylococcus aureus / Q000276:immunology*
D020382:Interleukin-18; D010457:Peptidoglycan; D012333:RNA, Messenger; D015847:Interleukin-4