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 (PPARγ) on mast cell function. However, there is no report about the role of PPARγ on differentiation of mast cells from the progenito...

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Bibliographic Details
Published in:Allergy (Copenhagen) 2008-09, Vol.63 (9), p.1136-1147
Main Authors: Tachibana, M., Wada, K., Katayama, K., Kamisaki, Y., Maeyama, K., Kadowaki, T., Blumberg, R. S., Nakajima, A.
Format: Article
Language:English
Subjects:
allergic disease
Animals
Biological and medical sciences
Bone marrow
Cell culture
Cell cycle
Dermatitis
Dermatitis, Atopic - metabolism
Dermatitis, Contact - metabolism
Dermatology
differentiation
Fundamental and applied biological sciences. Psychology
Fundamental immunology
GATA4 Transcription Factor - metabolism
GATA6 Transcription Factor - metabolism
Humans
Immune system
mast cell
Mast Cells - metabolism
Medical sciences
Mice
peroxisome proliferator‐activated receptor gamma
Peroxisomes - metabolism
PPAR gamma - metabolism
Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis
Skin involvement in other diseases. Miscellaneous. General aspects
Up-Regulation
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Summary:Background:  Mast cells play a central role in allergic and inflammatory diseases. Several reports indicated role of peroxisome proliferator‐activated receptor gamma (PPARγ) on mast cell function. However, there is no report about the role of PPARγ on differentiation of mast cells from the progenitors. In this study, we investigated the role of PPARγ 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 PPARγ, and in vivo murine dermatitis models. Results:  Activation of PPARγ 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 PPARγ 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. Conclusion:  Our results indicate that PPARγ is one of master regulators on mast cell maturation and potentially useful for the therapy in various disorders involving mast cell activation.
ISSN:0105-4538
1398-9995
DOI:10.1111/j.1398-9995.2008.01677.x