Activation of peroxisome proliferator-activated receptor gamma suppresses mast cell maturation involved in allergic diseases.
BACKGROUND
Mast cells play a central role in allergic and inflammatory diseases. Several reports indicated role of peroxisome proliferator-activated receptor gamma (PPARgamma) on mast cell function. However, there is no report about the role of PPARgamma on differentiation of mast cells from the progenitors. In this study, we investigated the role of PPARgamma in regulating bone marrow-derived mast cell maturation and the therapeutic implications for mast cell-related diseases such as atopic or contact dermatitis.


METHODS
We used in vitro cell culture system for mast cell differentiation from bone marrow-progenitors using specific ligands and lentiviral-mediated short hairpin RNA of PPARgamma, and in vivo murine dermatitis models.


RESULTS
Activation of PPARgamma inhibited the maturation of bone marrow progenitors into connective tissue-type mast cells (CTMCs) through up-regulation of GATA-4 and GATA-6 resulting in a decrease in expression of histidine decarboxylase and mast cell histamine content. In comparison, the differentiation of bone marrow progenitors into CTMCs was significantly accelerated by the knockdown of PPARgamma expression by lentiviral-mediated short hairpin RNA. Peroxisome proliferator-activated receptor gamma ligand administration to mice inhibited the maturation of mast cells resulting in attenuation of atopic and contact dermatitis via diminishment of the number of mature mast cells.


CONCLUSIONS
Our results indicate that PPARgamma is one of master regulators on mast cell maturation and potentially useful for the therapy in various disorders involving mast cell activation.
Gastroenterology Division, Yokohama City University School of Medicine, Yokohama, Japan.
M
M
Tachibana
K
K
Wada
K
K
Katayama
Y
Y
Kamisaki
K
K
Maeyama
T
T
Kadowaki
R S
RS
Blumberg
A
A
Nakajima
D000818:Animals; D003876:Dermatitis, Atopic / Q000378:metabolism*; D003877:Dermatitis, Contact / Q000378:metabolism*; D050991:GATA4 Transcription Factor / Q000378:metabolism; D050993:GATA6 Transcription Factor / Q000378:metabolism; D006801:Humans; D008407:Mast Cells / Q000378:metabolism*; D051379:Mice; D047495:PPAR gamma / Q000378:metabolism*; D020675:Peroxisomes / Q000378:metabolism*; D015854:Up-Regulation
D050991:GATA4 Transcription Factor; D050993:GATA6 Transcription Factor; D047495:PPAR gamma