Abrogation of lung inflammation in sensitized Stat6-deficient mice is dependent on the allergen inhalation procedure.
Conflicting results have been reported about the role of Stat6 in allergen-induced airway inflammation. We have studied the influence of the allergen inhalation procedure on the inflammatory response using wild-type and Stat6-deficient mice generated on a C57BL/6 background. Animals were immunized i.p. on day 0 and 7 with ovalbumin (OVA) and then received aerosolized OVA or phosphate buffer saline challenge (acute on day 14; chronic on day 14, 15, 16, 17 and 18) before being sacrificed at different time points. Following an acute challenge, Stat6-deficiency fully abrogated the increase in serum IgE levels and the development of lung inflammation (inflammatory cell infiltration, IL-4 and IL-5 release, and increase in plasma leakage). Following chronic challenge, despite the absence of IgE, IL-4 and IL-5, Stat6-deficient mice develop a characteristic lung inflammation, although the intensity was smaller when compared with the wild-type mice. OVA-induced early bronchoconstriction was observed in wild-type mice only after chronic challenge, and this was totally abrogated in the Stat6-deficient animals. These results suggest that Stat6 signalling is essential for the development of allergic airway inflammation following an acute allergen exposure. However, in a more chronic situation, the airway inflammatory response seems to be only partially mediated by Stat6.
Novartis Horsham Research Centre, Wimblehurst Road, Horsham, RH12 5AB.
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Trifilieff
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El-Hasim
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Corteling
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CE
Owen
D000485:Allergens / Q000276:immunology* / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D018893:Bronchoalveolar Lavage; D016084:Bronchoconstriction / Q000187:drug effects; D016207:Cytokines / Q000378:metabolism; D047209:Eosinophil Peroxidase; D005260:Female; D005353:Fibronectins / Q000378:metabolism; D007073:Immunoglobulin E / Q000097:blood; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010544:Peroxidases / Q000378:metabolism; D011014:Pneumonia / Q000276:immunology* / Q000378:metabolism / Q000503:physiopathology; D050800:STAT6 Transcription Factor; D015534:Trans-Activators / Q000172:deficiency / Q000276:immunology*
D000485:Allergens; D016207:Cytokines; D005353:Fibronectins; D050800:STAT6 Transcription Factor; C494100:Stat6 protein, mouse; D015534:Trans-Activators; D007073:Immunoglobulin E; D047209:Eosinophil Peroxidase; D010544:Peroxidases