Endogenous IL-33 Deficiency Exacerbates Liver Injury and Increases Hepatic Influx of Neutrophils in Acute Murine Viral Hepatitis
The alarmin IL-33 has been described to be upregulated in human and murine viral hepatitis. However, the role of endogenous IL-33 in viral hepatitis remains obscure. We aimed to decipher its function by infecting IL-33-deficient mice (IL-33 KO) and their wild-type (WT) littermates with pathogenic mo...
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| Format: | Article |
| Language: | English |
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Wiley
2017-01-01
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| Series: | Mediators of Inflammation |
| Online Access: | http://dx.doi.org/10.1155/2017/1359064 |
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| author | Virginie Carrière Muhammad Imran Arshad Jacques Le Seyec Benjamin Lefevre Muhammad Farooq Aurélien Jan Christelle Manuel Laurence Touami-Bernard Catherine Lucas-Clerc Valentine Genet Hugues Gascan Jean-Philippe Girard Frédéric Chalmel Lucie Lamontagne Claire Piquet-Pellorce Michel Samson |
| author_facet | Virginie Carrière Muhammad Imran Arshad Jacques Le Seyec Benjamin Lefevre Muhammad Farooq Aurélien Jan Christelle Manuel Laurence Touami-Bernard Catherine Lucas-Clerc Valentine Genet Hugues Gascan Jean-Philippe Girard Frédéric Chalmel Lucie Lamontagne Claire Piquet-Pellorce Michel Samson |
| author_sort | Virginie Carrière |
| collection | DOAJ |
| description | The alarmin IL-33 has been described to be upregulated in human and murine viral hepatitis. However, the role of endogenous IL-33 in viral hepatitis remains obscure. We aimed to decipher its function by infecting IL-33-deficient mice (IL-33 KO) and their wild-type (WT) littermates with pathogenic mouse hepatitis virus (L2-MHV3). The IL-33 KO mice were more sensitive to L2-MHV3 infection exhibiting higher levels of AST/ALT, higher tissue damage, significant weight loss, and earlier death. An increased depletion of B and T lymphocytes, NKT cells, dendritic cells, and macrophages was observed 48 h postinfection (PI) in IL-33 KO mice than that in WT mice. In contrast, a massive influx of neutrophils was observed in IL-33 KO mice at 48 h PI. A transcriptomic study of inflammatory and cell-signaling genes revealed the overexpression of IL-6, TNFα, and several chemokines involved in recruitment/activation of neutrophils (CXCL2, CXCL5, CCL2, and CCL6) at 72 h PI in IL-33 KO mice. However, the IFNγ was strongly induced in WT mice with less profound expression in IL-33 KO mice demonstrating that endogenous IL-33 regulated IFNγ expression during L2-MHV3 hepatitis. In conclusion, we demonstrated that endogenous IL-33 had multifaceted immunoregulatory effect during viral hepatitis via induction of IFNγ, survival effect on immune cells, and infiltration of neutrophils in the liver. |
| format | Article |
| id | doaj-art-9fe8ff11580440da92d3947ef6e69c6e |
| institution | Kabale University |
| issn | 0962-9351 1466-1861 |
| language | English |
| publishDate | 2017-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Mediators of Inflammation |
| spelling | doaj-art-9fe8ff11580440da92d3947ef6e69c6e2025-02-03T05:50:15ZengWileyMediators of Inflammation0962-93511466-18612017-01-01201710.1155/2017/13590641359064Endogenous IL-33 Deficiency Exacerbates Liver Injury and Increases Hepatic Influx of Neutrophils in Acute Murine Viral HepatitisVirginie Carrière0Muhammad Imran Arshad1Jacques Le Seyec2Benjamin Lefevre3Muhammad Farooq4Aurélien Jan5Christelle Manuel6Laurence Touami-Bernard7Catherine Lucas-Clerc8Valentine Genet9Hugues Gascan10Jean-Philippe Girard11Frédéric Chalmel12Lucie Lamontagne13Claire Piquet-Pellorce14Michel Samson15Institut National de la Santé et de la Recherche Médicale (Inserm), U.1085, Institut de Recherche Santé Environnement et Travail (IRSET), 35043 Rennes, FranceInstitut National de la Santé et de la Recherche Médicale (Inserm), U.1085, Institut de Recherche Santé Environnement et Travail (IRSET), 35043 Rennes, FranceInstitut National de la Santé et de la Recherche Médicale (Inserm), U.1085, Institut de Recherche Santé Environnement et Travail (IRSET), 35043 Rennes, FranceInstitut National de la Santé et de la Recherche Médicale (Inserm), U.1085, Institut de Recherche Santé Environnement et Travail (IRSET), 35043 Rennes, FranceInstitut National de la Santé et de la Recherche Médicale (Inserm), U.1085, Institut de Recherche Santé Environnement et Travail (IRSET), 35043 Rennes, FranceInstitut National de la Santé et de la Recherche Médicale (Inserm), U.1085, Institut de Recherche Santé Environnement et Travail (IRSET), 35043 Rennes, FranceInstitut National de la Santé et de la Recherche Médicale (Inserm), U.1085, Institut de Recherche Santé Environnement et Travail (IRSET), 35043 Rennes, FranceUniversité de Rennes 1, 35043 Rennes, FranceUniversité de Rennes 1, 35043 Rennes, FranceInstitut National de la Santé et de la Recherche Médicale (Inserm), U.1085, Institut de Recherche Santé Environnement et Travail (IRSET), 35043 Rennes, FranceInstitut de Génétique et Développement de Rennes (IGDR), UMR 6290 CNRS, Université de Rennes 1, 35043 Rennes, FranceInstitut de Pharmacologie et de Biologie Structurale, Centre National de la Recherche Scientifique (IPBS-CNRS), Université de Toulouse, 31077 Toulouse, FranceInstitut National de la Santé et de la Recherche Médicale (Inserm), U.1085, Institut de Recherche Santé Environnement et Travail (IRSET), 35043 Rennes, FranceDépartement des Sciences Biologiques, Université du Québec à Montréal, Montréal, QC, CanadaInstitut National de la Santé et de la Recherche Médicale (Inserm), U.1085, Institut de Recherche Santé Environnement et Travail (IRSET), 35043 Rennes, FranceInstitut National de la Santé et de la Recherche Médicale (Inserm), U.1085, Institut de Recherche Santé Environnement et Travail (IRSET), 35043 Rennes, FranceThe alarmin IL-33 has been described to be upregulated in human and murine viral hepatitis. However, the role of endogenous IL-33 in viral hepatitis remains obscure. We aimed to decipher its function by infecting IL-33-deficient mice (IL-33 KO) and their wild-type (WT) littermates with pathogenic mouse hepatitis virus (L2-MHV3). The IL-33 KO mice were more sensitive to L2-MHV3 infection exhibiting higher levels of AST/ALT, higher tissue damage, significant weight loss, and earlier death. An increased depletion of B and T lymphocytes, NKT cells, dendritic cells, and macrophages was observed 48 h postinfection (PI) in IL-33 KO mice than that in WT mice. In contrast, a massive influx of neutrophils was observed in IL-33 KO mice at 48 h PI. A transcriptomic study of inflammatory and cell-signaling genes revealed the overexpression of IL-6, TNFα, and several chemokines involved in recruitment/activation of neutrophils (CXCL2, CXCL5, CCL2, and CCL6) at 72 h PI in IL-33 KO mice. However, the IFNγ was strongly induced in WT mice with less profound expression in IL-33 KO mice demonstrating that endogenous IL-33 regulated IFNγ expression during L2-MHV3 hepatitis. In conclusion, we demonstrated that endogenous IL-33 had multifaceted immunoregulatory effect during viral hepatitis via induction of IFNγ, survival effect on immune cells, and infiltration of neutrophils in the liver.http://dx.doi.org/10.1155/2017/1359064 |
| spellingShingle | Virginie Carrière Muhammad Imran Arshad Jacques Le Seyec Benjamin Lefevre Muhammad Farooq Aurélien Jan Christelle Manuel Laurence Touami-Bernard Catherine Lucas-Clerc Valentine Genet Hugues Gascan Jean-Philippe Girard Frédéric Chalmel Lucie Lamontagne Claire Piquet-Pellorce Michel Samson Endogenous IL-33 Deficiency Exacerbates Liver Injury and Increases Hepatic Influx of Neutrophils in Acute Murine Viral Hepatitis Mediators of Inflammation |
| title | Endogenous IL-33 Deficiency Exacerbates Liver Injury and Increases Hepatic Influx of Neutrophils in Acute Murine Viral Hepatitis |
| title_full | Endogenous IL-33 Deficiency Exacerbates Liver Injury and Increases Hepatic Influx of Neutrophils in Acute Murine Viral Hepatitis |
| title_fullStr | Endogenous IL-33 Deficiency Exacerbates Liver Injury and Increases Hepatic Influx of Neutrophils in Acute Murine Viral Hepatitis |
| title_full_unstemmed | Endogenous IL-33 Deficiency Exacerbates Liver Injury and Increases Hepatic Influx of Neutrophils in Acute Murine Viral Hepatitis |
| title_short | Endogenous IL-33 Deficiency Exacerbates Liver Injury and Increases Hepatic Influx of Neutrophils in Acute Murine Viral Hepatitis |
| title_sort | endogenous il 33 deficiency exacerbates liver injury and increases hepatic influx of neutrophils in acute murine viral hepatitis |
| url | http://dx.doi.org/10.1155/2017/1359064 |
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