Overexpression of GATA-3 protects against the development of hypersensitivity pneumonitis.

Overexpression of GATA-3 protects against the development of hypersensitivity pneumonitis. Research Abstract Details 

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Overexpression of GATA-3 protects against the development of hypersensitivity pneumonitis. Abstract Text:

Yosuke Matsuno,Yukio Ishii,Keigyou Yoh,Yuko Morishima,Norihiro Haraguchi,Norihiro Kikuchi,Takashi Iizuka,Takumi Kiwamoto,Shinsuke Homma,Akihiro Nomura,Tohru Sakamoto,Morio Ohtsuka,Nobuyuki Hizawa,Satoru Takahashi,Yosuke Matsuno,Yukio Ishii,Keigyou Yoh,Yuko Morishima,Norihiro Haraguchi,Norihiro Kikuchi,Takashi Iizuka,Takumi Kiwamoto,Shinsuke Homma,Akihiro Nomura,Tohru Sakamoto,Morio Ohtsuka,Nobuyuki Hizawa,Satoru Takahashi,

RATIONALE: Hypersensitivity pneumonitis (HP) is mediated by a Th1 immune response. Transcription factor GATA binding protein-3 (GATA-3) is believed to be a key regulator of Th2 differentiation and thus might play regulatory roles in the pathogenesis of hypersensitivity pneumonitis (HP). OBJECTIVES: We examined the effect of GATA-3 overexpression on the development of HP in mice. METHODS: Wild-type C57BL/6 mice and GATA-3-overexpressing mice of the same background were used in this study. HP was induced by repeated exposure to Saccharopolyspora rectivirgula, the causative antigen of farmer's lung. MEASUREMENTS AND MAIN RESULTS: Antigen exposure resulted in a marked inflammatory response with enhanced pulmonary expression of T-bet and the Th1 cytokine interferon (IFN)-gamma in wild-type mice. The degree of pulmonary inflammation was much less severe in GATA-3-overexpressing mice. The induction of T-bet and IFN-gamma genes was suppressed, but a significant induction of Th2 cytokines, including IL-5 and IL-13, was observed in the lungs of GATA-3-overexpressing mice after antigen exposure. Supplementation with recombinant IFN-gamma enhanced lung inflammatory responses in GATA-3-overexpressing mice to the level of wild-type mice. Because antigen-induced IFN-gamma production predominantly occurred in CD4+ T cells, nude mice were transferred with CD4+ T cells from either wild-type or GATA-3-overexpressing mice and subsequently exposed to antigen. Lung inflammatory responses were significantly lower in nude mice transferred with CD4+ T cells from GATA-3-overexpressing mice than in those with wild-type CD4+ T cells, with a reduction of lung IFN-gamma level. CONCLUSIONS: These results indicate that overexpression of GATA-3 attenuates the development of HP by correcting the Th1-polarizing condition.

Overexpression of GATA-3 protects against the development of hypersensitivity pneumonitis. Publishing Authors By Initials

Y Matsuno,Y Ishii,K Yoh,Y Morishima,N Haraguchi,N Kikuchi,T Iizuka,T Kiwamoto,S Homma,A Nomura,T Sakamoto,M Ohtsuka,N Hizawa,S Takahashi,Y Matsuno,Y Ishii,K Yoh,Y Morishima,N Haraguchi,N Kikuchi,T Iizuka,T Kiwamoto,S Homma,A Nomura,T Sakamoto,M Ohtsuka,N Hizawa,S Takahashi,

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Overexpression of GATA-3 protects against the development of hypersensitivity pneumonitis. Journal Published:

PUBLICATION TYPE: Journal Article

Journal: American journal of respiratory and critical care

VOLUME: 176

Page Numbers: 1015-25

Journal Abbreviation: Am. J. Respir. Crit. Care Med.

ISSN: 1535-4970

DAY: 23

MONTH: 08

YEAR: 2007

Overexpression of GATA-3 protects against the development of hypersensitivity pneumonitis. Information

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LANGUAGE: eng

NlmUniqueID: 9421642

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AFFILIATION: Department of Respiratory Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan.

Country: United States

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MEDLINETA: Am J Respir Crit Care Med

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