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Mice deficient in epidermal PPARγ exhibit loss of sebaceous glands as well as augmented apoptosis and inflammation in response to ultraviolet B
Author(s) -
Konger Raymond Lloyd,
Martel Kellie C,
DaSilva Sonia C,
Sahu Ravi P
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.348.9
Subject(s) - inflammation , epidermis (zoology) , apoptosis , cancer research , peroxisome proliferator activated receptor , tumor necrosis factor alpha , biology , endocrinology , immunology , medicine , chemistry , receptor , biochemistry , anatomy
Previous pharmacological studies have provided conflicting results regarding the relevance of PPARγ in photobiology. In these current studies, we utilize a cytokeratin 14 promoter driven CRE‐LoxP strategy to examine how loss of epidermal PPARγ (KO mice) alters ultraviolet B (UVB) responses in mouse skin. We first demonstrate an increase in PPARγ ligand production in lipid extracts of mouse epidermis irradiated with 1500 J/m 2 of UVB. We next show that after 24 hrs, KO mice exhibit a marked increase (> 4‐fold) in UVB‐induced apoptosis as measured by epidermal caspase 3 activity. We next assessed UVB‐induced inflammatory responses. At 24 and 72 hrs post‐irradiation, KO mice exhibited increased inflammation as determined by significant increases in skin thickness, myeloperoxidase activity and inflammatory cell infiltrates. Given that inflammatory infiltrates typically occur at 36–48 hrs post‐UVB, these studies suggest an earlier onset of inflammation in KO mice. Finally, in data unrelated to UVB irradiation, adult KO mice also exhibited almost complete loss of sebaceous glands. This data provides compelling evidence that epidermal PPARγ serves an important role in regulating the acute epidermal photoresponse and is necessary for sebaceous gland development and/or maintenance. Supported by funding by the National Institutes of Health and the Prevent Cancer Foundation.