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

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 up-regulation of SOCS1 after IL-13 stimulation.

CONCLUSIONS:

SOCS1 induction by IL-13 in airway structural cells is critical to negatively control allergic airway disease.

• Authors: 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
• Journal: American journal of respiratory and critical care medicine (Am J Respir Crit Care Med) Vol. 179 Issue 11 Pg. 992-8 (Jun 01 2009) ISSN: 1535-4970 [Electronic] United States
• PMID: 19299500 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Interleukin-13
• SOCS1 protein, human
• STAT6 Transcription Factor
• STAT6 protein, human
• Socs1 protein, mouse
• Stat6 protein, mouse
• Suppressor of Cytokine Signaling 1 Protein
• Suppressor of Cytokine Signaling Proteins

Topics

• Animals
• Asthma (immunology)
• Cells, Cultured
• Disease Models, Animal
• Humans
• Interleukin-13 (immunology)
• Mice
• Myocytes, Smooth Muscle (immunology)
• STAT6 Transcription Factor (metabolism)
• Suppressor of Cytokine Signaling 1 Protein
• Suppressor of Cytokine Signaling Proteins (immunology, metabolism)
• Th2 Cells (immunology)
• Up-Regulation