Pulmonary suppressor of cytokine signaling-1 induced by IL-13 regulates allergic asthma phenotype

Fukuyama, S; Nakano, T; Matsumoto, T; Oliver, BGG; Burgess, JK; Moriwaki, A; Tanaka, K; Kubo, M; Hoshino, T; Tanaka, H; McKenzie, ANJ; Matsumoto, K; Aizawa, H; Nakanishi, Y; Yoshimura, A; Black, JL; Inoue, H

Pulmonary suppressor of cytokine signaling-1 induced by IL-13 regulates allergic asthma phenotype

Fukuyama, S Nakano, T Matsumoto, T Oliver, BGG

Burgess, JK Moriwaki, A Tanaka, K Kubo, M Hoshino, T Tanaka, H McKenzie, ANJ Matsumoto, K Aizawa, H Nakanishi, Y Yoshimura, A Black, JL Inoue, H

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Publication Type:: Journal Article
Citation:: American Journal of Respiratory and Critical Care Medicine, 2009, 179 (11), pp. 992 - 998
Issue Date:: 2009-06-01

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Field	Value	Language
dc.contributor.author	Fukuyama, S	en_US
dc.contributor.author	Nakano, T	en_US
dc.contributor.author	Matsumoto, T	en_US
dc.contributor.author	Oliver, BGG https://orcid.org/0000-0002-7122-9262	en_US
dc.contributor.author	Burgess, JK	en_US
dc.contributor.author	Moriwaki, A	en_US
dc.contributor.author	Tanaka, K	en_US
dc.contributor.author	Kubo, M	en_US
dc.contributor.author	Hoshino, T	en_US
dc.contributor.author	Tanaka, H	en_US
dc.contributor.author	McKenzie, ANJ	en_US
dc.contributor.author	Matsumoto, K	en_US
dc.contributor.author	Aizawa, H	en_US
dc.contributor.author	Nakanishi, Y	en_US
dc.contributor.author	Yoshimura, A	en_US
dc.contributor.author	Black, JL	en_US
dc.contributor.author	Inoue, H	en_US
dc.date.issued	2009-06-01	en_US
dc.identifier.citation	American Journal of Respiratory and Critical Care Medicine, 2009, 179 (11), pp. 992 - 998	en_US
dc.identifier.issn	1073-449X	en_US
dc.identifier.uri	http://hdl.handle.net/10453/28547
dc.description.abstract	Rationale: Th2 cytokines play an important role in allergic diseases. These cytokines activate signal transduction pathways, including Janus kinase/signal transducer and activator of transcription (STAT) signaling. Although the suppressor of cytokine signaling (SOCS) family protein, a negative regulator of the Janus kinase/STAT signaling pathway, contributes to helper T cell differentiation during immune responses, the role of SOCS proteins within the structural cells of a target organ has not been clarified in allergy. Objectives: To study the local function of SOCS in the development of asthma. Methods: We used mouse models of IL-13- and ovalbumin (OVA)-induced allergic airway disease. Airway smooth muscle cells were cultured from patients with asthma. Measurements and Main Results: The administration of IL-13 induced not only airway responses but also SOCS1 expression at the local inflammatory site. The up-regulated SOCS1 markedly suppressed IL-13-dependent STAT6 activation and eotaxin expression and subsequently down-regulated IL-13-induced airway inflammatory responses. The inactivation of SOCS1 induced airway hyperresponsiveness after IL-13 treatment even in hyporesponsive C57BL/6 background mice. In an OVA-induced model of allergic airway disease, allergen exposure up-regulated local SOCS1 expression, and the induction of SOCS1 in the airways attenuated allergen-induced airway responses. Inactivation of IL-13 inhibited SOCS1 induction in a model of allergic airway disease. Interestingly, airway smooth muscle cells from individuals with asthma had impaired upregulation of SOCS1 after IL-13 stimulation. Conclusions: SOCS1 induction by IL-13 in airway structural cells is critical to negatively control allergic airway disease.	en_US
dc.relation.ispartof	American Journal of Respiratory and Critical Care Medicine	en_US
dc.relation.isbasedon	10.1164/rccm.200806-992OC	en_US
dc.subject.classification	Respiratory System	en_US
dc.subject.mesh	Th2 Cells	en_US
dc.subject.mesh	Cells, Cultured	en_US
dc.subject.mesh	Myocytes, Smooth Muscle	en_US
dc.subject.mesh	Animals	en_US
dc.subject.mesh	Humans	en_US
dc.subject.mesh	Mice	en_US
dc.subject.mesh	Asthma	en_US
dc.subject.mesh	Disease Models, Animal	en_US
dc.subject.mesh	Interleukin-13	en_US
dc.subject.mesh	Up-Regulation	en_US
dc.subject.mesh	STAT6 Transcription Factor	en_US
dc.subject.mesh	Suppressor of Cytokine Signaling Proteins	en_US
dc.subject.mesh	Suppressor of Cytokine Signaling 1 Protein	en_US
dc.title	Pulmonary suppressor of cytokine signaling-1 induced by IL-13 regulates allergic asthma phenotype	en_US
dc.type	Journal Article
utslib.citation.volume	11	en_US
utslib.citation.volume	179	en_US
utslib.for	1102 Cardiorespiratory Medicine and Haematology	en_US
utslib.for	11 Medical and Health Sciences	en_US
pubs.embargo.period	Not known	en_US
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Science
pubs.organisational-group	/University of Technology Sydney/Faculty of Science/School of Life Sciences
pubs.organisational-group	/University of Technology Sydney/Strength - CHT - Health Technologies
utslib.copyright.status	closed_access
pubs.issue	11	en_US
pubs.publication-status	Published	en_US
pubs.volume	179	en_US

Abstract:

Rationale: Th2 cytokines play an important role in allergic diseases. These cytokines activate signal transduction pathways, including Janus kinase/signal transducer and activator of transcription (STAT) signaling. Although the suppressor of cytokine signaling (SOCS) family protein, a negative regulator of the Janus kinase/STAT signaling pathway, contributes to helper T cell differentiation during immune responses, the role of SOCS proteins within the structural cells of a target organ has not been clarified in allergy. Objectives: To study the local function of SOCS in the development of asthma. Methods: We used mouse models of IL-13- and ovalbumin (OVA)-induced allergic airway disease. Airway smooth muscle cells were cultured from patients with asthma. Measurements and Main Results: The administration of IL-13 induced not only airway responses but also SOCS1 expression at the local inflammatory site. The up-regulated SOCS1 markedly suppressed IL-13-dependent STAT6 activation and eotaxin expression and subsequently down-regulated IL-13-induced airway inflammatory responses. The inactivation of SOCS1 induced airway hyperresponsiveness after IL-13 treatment even in hyporesponsive C57BL/6 background mice. In an OVA-induced model of allergic airway disease, allergen exposure up-regulated local SOCS1 expression, and the induction of SOCS1 in the airways attenuated allergen-induced airway responses. Inactivation of IL-13 inhibited SOCS1 induction in a model of allergic airway disease. Interestingly, airway smooth muscle cells from individuals with asthma had impaired upregulation of SOCS1 after IL-13 stimulation. Conclusions: SOCS1 induction by IL-13 in airway structural cells is critical to negatively control allergic airway disease.

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http://hdl.handle.net/10453/28547