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Publication : Characterization of immune responses and the lung transcriptome in a murine model of IL-33 challenge.

First Author  Piyadasa H Year  2020
Journal  Biochim Biophys Acta Mol Basis Dis Volume  1866
Issue  12 Pages  165950
PubMed ID  32841733 Mgi Jnum  J:301014
Mgi Id  MGI:6504174 Doi  10.1016/j.bbadis.2020.165950
Citation  Piyadasa H, et al. (2020) Characterization of immune responses and the lung transcriptome in a murine model of IL-33 challenge. Biochim Biophys Acta Mol Basis Dis 1866(12):165950
abstractText  IL-33 induces airway inflammation and hyper-responsiveness in respiratory diseases. Although defined as a therapeutic target, there are limited studies that have comprehensively investigated IL-33-mediated responses in the lungs in vivo. In this study, we characterized immunological and physiological responses induced by intranasal IL-33 challenge, in a mouse model. We identified specific cytokines, IL-4, IL-5, IL-6, IL-10, IP-10 and MIP1-alpha, that are increased in bronchoalveolar lavage and lung tissues by IL-33. Using transcriptomics (RNA-Seq) we demonstrated that 2279 transcripts were up-regulated and 1378 downregulated (>/= 2-fold, p < 0.01) in lung tissues, in response to IL-33. Bioinformatic interrogation of the RNA-Seq data was used to predict biological pathways and upstream regulators involved in IL-33-mediated responses. We showed that the mRNA and protein of STAT4, a predicted upstream regulator of IL-33-induced transcripts, was significantly enhanced in the lungs following IL-33 challenge. Overall, this study provides specific IL-33-induced molecular targets and endpoints that can be used as a resource for in vivo studies, e.g. in preclinical murine models examining novel interventions to target downstream effects of IL-33.
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