- Title
- Mechanism of interleukin-25 (IL-17E)-induced pulmonary inflammation and airways hyper-reactivity
- Creator
- Sharkhuu, T.; Matthaei, K. I.; Forbes, E.; Mahalingam, S.; Hogan, S. P.; Hansbro, P. M.; Foster, P. S.
- Relation
- NHMRC.224206
- Relation
- Clinical and Experimental Allergy Vol. 36, Issue 12, p. 1575-1583
- Publisher Link
- http://dx.doi.org/10.1111/j.1365-2222.2006.02595.x
- Publisher
- Wiley-Blackwell
- Resource Type
- journal article
- Date
- 2006
- Description
- Background: IL-25, a novel member of the IL-17 cytokine family, promotes CD4+ T-helper 2 lymphocyte-like (Th type-2) inflammatory responses in the lung. Although IL-25 up-regulates IL-13 in the lung, the contribution of this and other type 2 cytokine signalling pathways to the induction and persistence of airways hyper-reactivity (AHR) and allergic inflammation are unclear. Objective: To determine the downstream factors employed by IL-25 to induce Th type-2 pulmonary inflammation and AHR. Methods: IL-25 was delivered to the airways of BALB/c mice by intra-tracheal (i.t.) instillation and AHR and Th type-2 inflammatory responses were characterized in wild type (WT) and Th type-2-cytokine and -signalling pathway-deficient (−/−) mice. Results: IL-25 treatment resulted in AHR, eosinophilic inflammation, mucus hypersecretion and a progressive increase in the production of Th type-2 cytokines in the lungs. Levels of arginase-I (arg-I) and eotaxin were also elevated by IL-25 treatment. A significant reduction in AHR, and attenuation of mucus production was observed in IL-25-treated IL-13−/−, IL-4 receptor alpha (IL-4Rα−/−)- and signal-transducer-and-activator-of-transcription-factor-6 (STAT6−/−)-deficient mice. AHR was also inhibited in IL-4−/−- and IL-5/eotaxin(1)−/−- deficient mice treated with IL-25, however, mucus hypersecretion was not completely ablated. IL-25 promoted Th type-2 responses by directly acting on naïve T cells. Conclusion: IL-25 potently (single dose) induces sustained AHR and acute pulmonary inflammation with eosinophilia. IL-25-induced AHR is dependent on the production of Th type-2 cytokines, and removal of IL-13 and its signal transduction pathway prevents IL-25-induced airways inflammation and AHR. IL-25 potently induces inflammatory cascades that may exacerbate allergic airways inflammation by promoting Th type-2 cytokine responses in conjunction with the up-regulation of factors (eotaxin and arg-I) that can amplify inflammation associated with allergic disorders. Dysregulation in IL-25 production may predispose to features of allergic airways disease.
- Subject
- allergy/asthma; inflammation; interleukins; mouse model
- Identifier
- http://hdl.handle.net/1959.13/1310915
- Identifier
- uon:22117
- Identifier
- ISSN:0954-7894
- Language
- eng
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