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Peptidoglycan Synergistically Augments Production of Allergic Mediators from Murine Mast Cells in Combination with Muramyldipeptide

Katsuhiko Matsui, Keisuke Shigehara and Reiko Ikeda

Background: Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by superficial Staphylococcus aureus colonization and an increased number of mast cells in the lesional skin, the immunopathologic features varying according to lesion duration.

Objective: The present study was conducted to clarify the effects of S. aureus cell wall components on production of allergic mediators from murine mast cells.

Methods: Peptidoglycan (PEG) and/or muramyldipeptide (MDP) were/was used to stimulate murine mast cells, and the resulting culture supernatants were assayed for Th1 and Th2 chemokines and histamine release. Chemokine production was assessed using reverse transcription-polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA). Histamine release was measured using a competitive ELISA.

Results: PEG stimulation induced production of the Th1 chemokine, CXCL10, and the Th2 chemokine, CCL17 by mast cells. Although MDP did not induce production of these chemokines, it synergistically enhanced the PEG-stimulated production of CCL17, but not CXCL10, from the mast cells. Histamine release was also enhanced in the presence of MDP.

Conclusion: The present results suggest that, in AD patients, S. aureus colonization may exacerbate acute allergic inflammation through up-regulation of CCL17 production and histamine release from PEG- and MDP-stimulated mast cells.