Abstracts (complete list) - Wissenschaft Online

Anja Dahten, Dennis Ernst, Dana Hoser, Margitta Worm
PPARγ-ligation improves development of allergen-induced
skin inflammation in a murine model of dermatitis
Background: Recent studies point to the pathophysiological role of the nuclear receptor
PPARγ in the inflammatory immune response. We have previously shown that a specific
ligand of PPARγ attenuates the systemic immune response via regulation of humoral
immunity and inhibition of T cell-derived inflammatory cytokine production. The
objective of this study was to investigate the impact of PPARγ-ligand treatment on the
local immune response in a murine dermatitis model. Methods: We established a murine
model with reproducible, OVA-induced skin inflammation. In this model PPARγ-ligand
was applied at different time points via intraperitoneal or epicutaneous routes. Skin and
blood samples were obtained for analysis respectively. Affected skin areas were
assessed by a standardised clinical skin score (CSS), histological and
immunohistochemical analysis. OVA-specific IgE, IgG1 and IgG2a levels were measured
by ELISA on different time points (day 1, 21, 35 and 70). Results: Systemic application
of PPARγ-ligand reduced the severity of OVA-induced eczematous skin lesions up to
70%. These observations were confirmed by histological examinations of skin biopsies,
showing decreased thickness of dermis and epidermis (p < 0.001) accompanied by
significantly reduced infiltration of CD4 and CD8 positive lymphocytes and mast cells.
OVA-specific IgE and IgG1 responses were significantly inhibited on days 21/35, but
IgG2a synthesis was not affected. Conclusion: Our results demonstrate PPARγ-ligand
treatment inhibits the development of allergen-mediated dermatitis by local and
systemic mechanisms. These findings are important for the development of novel
therapeutic strategies involving a PPARγ-ligand based treatment in allergic diseases.