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Overexpression of suppressor of cytokine signalling-5 augments eosinophilic airway inflammation in mice
Authors:M. Ohshima  A. Yokoyama  H. Ohnishi  H. Hamada  N. Kohno  J. Higaki   T. Naka
Affiliation:Internal Medicine II, Ehime University School of Medicine, Tohon, Ehime, Japan.
Abstract:BACKGROUND: Enhanced expression of the suppressor of cytokine signalling (SOCS)-5 might be of therapeutic benefit for T-helper type 2 (Th2) dominant diseases, as its expression is reported to result in a reduction of Th2 differentiation in vitro due to the inhibition of IL-4 signalling. OBJECTIVE: To investigate the regulatory role of SOCS-5 in vivo, we explored the phenotype of an experimental asthma model developed in SOCS-5 transgenic (Tg) mice. METHODS: The SOCS-5 Tg mice or wild-type (WT) mice were sensitized and repeatedly challenged with ovalbumin (OVA). We examined bronchoalveolar lavage fluid (BALF), lung specimens, and airway hyperresponsiveness (AHR) to methacholine. RESULTS: The production of IFN-gamma by CD4(+) T cells from unprimed SOCS-5 Tg mice was significantly increased in comparison with unprimed wild-type mice, indicating that SOCS-5 Tg mice have a Th1-polarizing condition under natural conditions. However, in an asthma model, significantly more eosinophils in the airways and higher levels of IL-5 and IL-13 in BALF were observed in the SOCS-5 Tg than the wild-type mice. AHR in the asthma model of SOCS-5 Tg was also more enhanced than that of wild-type mice. OVA-stimulated CD4(+) T cells from the primed SOCS-5 Tg mice produced significantly more IL-5 and IL-13 than CD4(+) T cells from wild-type mice. CONCLUSION: Our results demonstrate that the overexpression of SOCS-5 does not inhibit Th2 response, but rather augments the phenotype of the asthma model in vivo. This finding throws into question the therapeutic utility of using enhancement of SOCS-5 expression for Th2-dominant disease.
Keywords:asthma    CD4+ T cells    cytokines    epidermal growth factor    rodent
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