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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.

journal_name

Am J Respir Crit Care Med

journal_title

American journal of respiratory and critical care medicine

authors

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

doi

10.1164/rccm.200806-992OC

subject

Has Abstract

pub_date

2009-06-01 00:00:00

pages

992-8

issue

eissn

1073-449X

issn

1535-4970

pii

200806-992OC

journal_volume

179

pub_type

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