Activation of peroxisome proliferator-activated receptor gamma suppresses mast cell maturation involved in allergic diseases

被引：41

作者：

Tachibana, M. ^{[2
]}

Wada, K. ^{[1
]}

Katayama, K. ^{[3
]}

Kamisaki, Y. ^{[1
]}

Maeyama, K. ^{[4
]}

Kadowaki, T. ^{[5
]}

Blumberg, R. S. ^{[6
,7
]}

Nakajima, A. ^{[2
,6
,7
]}

机构：

[1] Osaka Univ, Dept Pharmacol, Grad Sch Dent, Suita, Osaka 5650871, Japan

[2] Yokohama City Univ, Sch Med, Div Gastroenterol, Yokohama, Kanagawa 232, Japan

[3] Tokyo Metropolitan Inst Med Sci, Dept Allergy & Immunol, Tokyo 113, Japan

[4] Ehime Univ, Sch Med, Dept Pharmacol, Matsuyama, Ehime 790, Japan

[5] Univ Tokyo, Bunkyo Ku, Dept Metab Dis, Grad Sch Med, Tokyo 113, Japan

[6] Brigham & Womens Hosp, Div Gastroenterol, Dept Med, Boston, MA 02115 USA

[7] Harvard Univ, Sch Med, Boston, MA USA

来源：

ALLERGY | 2008年 / 63卷 / 09期

关键词：

allergic disease; differentiation; dermatitis; mast cell; peroxisome proliferator-activated receptor gamma;

D O I：

10.1111/j.1398-9995.2008.01677.x

中图分类号：

R392 [医学免疫学];

学科分类号：

100102 ;

摘要：

Background: Mast cells play a central role in allergic and inflammatory diseases. Several reports indicated role of peroxisome proliferator-activated receptor gamma (PPAR gamma) on mast cell function. However, there is no report about the role of PPAR gamma on differentiation of mast cells from the progenitors. In this study, we investigated the role of PPAR gamma 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 PPAR gamma, and in vivo murine dermatitis models. Results: Activation of PPAR gamma 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 PPAR gamma 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 PPAR gamma is one of master regulators on mast cell maturation and potentially useful for the therapy in various disorders involving mast cell activation.

引用

页码：1136 / 1147

页数：12

共 24 条

[1] Regulated expression of GATA-6 transcription factor in gastric endocrine cells [J].