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            <title xml:lang="en">Infection with influenza virus induces IL-33 in murine lungs.</title>
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            <funder>This work was supported by Institut National de la Sante Et de la Recherche Medicale, the Institut National de la Recherche Agronomique, the Ministere de l'Education Nationale de la Recherche et de la Technologie, Region Bretagne, the Ligue contre le Cancer, and Institut Federatif de Recherche 140. M.I.A. was supported by a doctoral fellowship from the Government of Pakistan (via the Higher Education Commission, University of Agriculture, Faisalabad, Pakistan).</funder>
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                <title level="j">American Journal of Respiratory Cell and Molecular Biology</title>
                <imprint>
                  <publisher>American Thoracic Society</publisher>
                  <biblScope unit="volume">45</biblScope>
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                <term xml:lang="en">influenza virus</term>
                <term xml:lang="en">pulmonary infection</term>
                <term xml:lang="en">biochemistry and molecular biology</term>
                <term xml:lang="en">respiratory system</term>
                <term xml:lang="fr">IL-33</term>
                <term xml:lang="fr">cell biology</term>
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              <classCode scheme="mesh">Bronchoalveolar Lavage</classCode>
              <classCode scheme="mesh">Interferon-beta</classCode>
              <classCode scheme="mesh">Interferon-gamma</classCode>
              <classCode scheme="mesh">Interleukin-1beta</classCode>
              <classCode scheme="mesh">Interleukin-6</classCode>
              <classCode scheme="mesh">Interleukins</classCode>
              <classCode scheme="mesh">Lung</classCode>
              <classCode scheme="mesh">Mice</classCode>
              <classCode scheme="mesh">Orthomyxoviridae Infections</classCode>
              <classCode scheme="mesh">RNA, Messenger</classCode>
              <classCode scheme="mesh">Tumor Necrosis Factor-alpha</classCode>
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              <classCode scheme="mesh">Animals</classCode>
              <classCode scheme="mesh">Endothelial Cells</classCode>
              <classCode scheme="mesh">Epithelial Cells</classCode>
              <classCode scheme="mesh">Female</classCode>
              <classCode scheme="mesh">Gene Expression Regulation</classCode>
              <classCode scheme="mesh">Humans</classCode>
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              <p>IL-33, a novel IL-1 family member, is crucially expressed and involved in pulmonary diseases, but its regulation in viral diseases such as influenza A virus (IAV) remains unclear. This study aimed to characterize the expression and release of IL-33 in lungs of IAV-infected mice in vivo and in murine respiratory epithelial cells (MLE-15) in vitro. Our results provide evidence of up-regulation of IL-33 mRNA in IAV-infected murine lungs, compared with noninfected control mice. The overexpression of IL-33 was positively correlated with a significant increase in mRNA encoding the proinflammatory cytokines TNF-α, IFN-γ, IL-1β, and IL-6, and was also associated with an increase in IFN-β mRNA. A profound overexpression of IL-33 protein was evident in IAV-infected murine lungs and bronchoalveolar lavages of influenza-infected mice, compared with low concentrations in naive lungs in vivo. Immunolocalization highlighted the cellular expression of IL-33 in alveolar epithelial and endothelial cells, along with increased infiltrate cells in virus-infected lungs. Further in vitro experiments showed an induction of IL-33 transcript-in MLE-15 cells and human epithelial cells (A549) infected with different strains of IAV in comparison with noninfected cells. In conclusion, our findings evidenced a profound expression of IL-33 in lungs during both in vivo and in vitro IAV infections, suggesting a role for IL-33 in virus-induced lung infections.</p>
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