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Activation of peroxisome proliferator-activated receptor gamma suppresses mast cell maturation involved in allergic diseases |
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| Authors: | Tachibana M Wada K Katayama K Kamisaki Y Maeyama K Kadowaki T Blumberg R S Nakajima A |
| Affiliation: | Gastroenterology Division, Yokohama City University School of Medicine, Yokohama, Japan;;Department of Pharmacology, Graduate School of Dentistry, Osaka University, Suita, Osaka, Japan;;Department of Allergy and Immunology, The Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan;;Department of Pharmacology, Ehime University School of Medicine, Onsen-gun, Ehime, Japan;;Department of Metabolic Diseases, Graduate School of Medicine, University of Tokyo, Bunkyo-ku, Tokyo, Japan;;Gastroenterology Division, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA |
| Abstract: | 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. |
| Keywords: | allergic disease differentiation dermatitis mast cell peroxisome proliferator-activated receptor gamma |
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