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


OBJECTIVE
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.


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.
Fukuyama
Satoru
S
Research Institute for Diseases of the Chest, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
Nakano
Takako
T
Matsumoto
Takafumi
T
Oliver
Brian G G
BG
Burgess
Janette K
JK
Moriwaki
Atsushi
A
Tanaka
Kentaro
K
Kubo
Masato
M
Hoshino
Tomoaki
T
Tanaka
Hiroyuki
H
McKenzie
Andrew N J
AN
Matsumoto
Koichiro
K
Aizawa
Hisamichi
H
Nakanishi
Yoichi
Y
Yoshimura
Akihiko
A
Black
Judith L
JL
Inoue
Hiromasa
H
D000818:Animals; D001249:Asthma / Q000276:immunology*; D002478:Cells, Cultured; D004195:Disease Models, Animal; D006801:Humans; D018793:Interleukin-13 / Q000276:immunology*; D051379:Mice; D032389:Myocytes, Smooth Muscle / Q000276:immunology*; D050800:STAT6 Transcription Factor / Q000378:metabolism; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000276:immunology* / Q000378:metabolism*; D018418:Th2 Cells / Q000276:immunology; D015854:Up-Regulation
D018793:Interleukin-13; C108944:SOCS1 protein, human; D050800:STAT6 Transcription Factor; C494101:STAT6 protein, human; C491590:Socs1 protein, mouse; C494100:Stat6 protein, mouse; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins