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

Satoru Fukuyama, Takako Nakano, Takafumi Matsumoto, Brian G.G. Oliver, Janette K. Burgess, Atsushi Moriwaki, Kentaro Tanaka, Masato Kubo, Tomoaki Hoshino, Hiroyuki Tanaka, Andrew N.J. McKenzie, Koichiro Matsumoto, Hisamichi Aizawa, Yoichi Nakanishi, Akihiko Yoshimura, Judith L. Black, Hiromasa Inoue

研究成果: Article査読

27 被引用数 (Scopus)


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.

ジャーナルAmerican journal of respiratory and critical care medicine
出版ステータスPublished - 2009 6月 1

ASJC Scopus subject areas

  • 呼吸器内科
  • 集中医療医学


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