| First Author | Fukuyama S | Year | 2009 |
| Journal | Am J Respir Crit Care Med | Volume | 179 |
| Issue | 11 | Pages | 992-8 |
| PubMed ID | 19299500 | Mgi Jnum | J:164975 |
| Mgi Id | MGI:4835843 | Doi | 10.1164/rccm.200806-992OC |
| Citation | Fukuyama S, et al. (2009) Pulmonary suppressor of cytokine signaling-1 induced by IL-13 regulates allergic asthma phenotype. Am J Respir Crit Care Med 179(11):992-8 |
| abstractText | 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. |
