IL-38 Alleviates Inflammation in Sepsis in Mice by Inhibiting Macrophage Apoptosis and Activation of the NLRP3 Inflammasome
Interleukin- (IL-) 38 is an emerging cytokine with multiple functions involved in infection and immunity. However, the potential role of IL-38 in the host immune response during sepsis remains elusive. Herein, we investigated if macrophages in septic mice express IL-38, the molecular mechanisms behi...
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| Format: | Article |
| Language: | English |
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Wiley
2021-01-01
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| Series: | Mediators of Inflammation |
| Online Access: | http://dx.doi.org/10.1155/2021/6370911 |
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| author | Yun Ge Juan Chen Yanting Hu Xinyi Chen Man Huang |
| author_facet | Yun Ge Juan Chen Yanting Hu Xinyi Chen Man Huang |
| author_sort | Yun Ge |
| collection | DOAJ |
| description | Interleukin- (IL-) 38 is an emerging cytokine with multiple functions involved in infection and immunity. However, the potential role of IL-38 in the host immune response during sepsis remains elusive. Herein, we investigated if macrophages in septic mice express IL-38, the molecular mechanisms behind its expression, and the downstream effects of its expression. In mouse peritoneal macrophages, lipopolysaccharide (LPS) upregulated IL-38 and its receptor IL-36R, and the resulting IL-38 shifted macrophages from a M1 to M2 phenotype. Moreover, exposure to IL-38 alone was sufficient to inhibit macrophage apoptosis and LPS-driven activation of the NOD-, LRR-, and pyrin domain-containing 3 (NLRP3) inflammasome. These effects were partly abrogated by IL-38 downregulation. In septic mice, IL-38 markedly lowered serum concentrations of proinflammatory cytokines and greatly improved survival. Conversely, IL-38 blockade aggravated their mortality. Collectively, these findings present IL-38 as a potent immune modulator that restrains the inflammatory response by suppressing macrophage apoptosis and activation of the NLRP3 inflammasome. IL-38 may help protect organs from sepsis-related injury. |
| format | Article |
| id | doaj-art-2dd7cd8632d6405c9a926f62ef2aa6ec |
| institution | Kabale University |
| issn | 1466-1861 |
| language | English |
| publishDate | 2021-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Mediators of Inflammation |
| spelling | doaj-art-2dd7cd8632d6405c9a926f62ef2aa6ec2025-08-20T03:55:06ZengWileyMediators of Inflammation1466-18612021-01-01202110.1155/2021/6370911IL-38 Alleviates Inflammation in Sepsis in Mice by Inhibiting Macrophage Apoptosis and Activation of the NLRP3 InflammasomeYun Ge0Juan Chen1Yanting Hu2Xinyi Chen3Man Huang4Department of General Intensive Care UnitDepartment of General Intensive Care UnitDepartment of General Intensive Care UnitDepartment of General Intensive Care UnitDepartment of General Intensive Care UnitInterleukin- (IL-) 38 is an emerging cytokine with multiple functions involved in infection and immunity. However, the potential role of IL-38 in the host immune response during sepsis remains elusive. Herein, we investigated if macrophages in septic mice express IL-38, the molecular mechanisms behind its expression, and the downstream effects of its expression. In mouse peritoneal macrophages, lipopolysaccharide (LPS) upregulated IL-38 and its receptor IL-36R, and the resulting IL-38 shifted macrophages from a M1 to M2 phenotype. Moreover, exposure to IL-38 alone was sufficient to inhibit macrophage apoptosis and LPS-driven activation of the NOD-, LRR-, and pyrin domain-containing 3 (NLRP3) inflammasome. These effects were partly abrogated by IL-38 downregulation. In septic mice, IL-38 markedly lowered serum concentrations of proinflammatory cytokines and greatly improved survival. Conversely, IL-38 blockade aggravated their mortality. Collectively, these findings present IL-38 as a potent immune modulator that restrains the inflammatory response by suppressing macrophage apoptosis and activation of the NLRP3 inflammasome. IL-38 may help protect organs from sepsis-related injury.http://dx.doi.org/10.1155/2021/6370911 |
| spellingShingle | Yun Ge Juan Chen Yanting Hu Xinyi Chen Man Huang IL-38 Alleviates Inflammation in Sepsis in Mice by Inhibiting Macrophage Apoptosis and Activation of the NLRP3 Inflammasome Mediators of Inflammation |
| title | IL-38 Alleviates Inflammation in Sepsis in Mice by Inhibiting Macrophage Apoptosis and Activation of the NLRP3 Inflammasome |
| title_full | IL-38 Alleviates Inflammation in Sepsis in Mice by Inhibiting Macrophage Apoptosis and Activation of the NLRP3 Inflammasome |
| title_fullStr | IL-38 Alleviates Inflammation in Sepsis in Mice by Inhibiting Macrophage Apoptosis and Activation of the NLRP3 Inflammasome |
| title_full_unstemmed | IL-38 Alleviates Inflammation in Sepsis in Mice by Inhibiting Macrophage Apoptosis and Activation of the NLRP3 Inflammasome |
| title_short | IL-38 Alleviates Inflammation in Sepsis in Mice by Inhibiting Macrophage Apoptosis and Activation of the NLRP3 Inflammasome |
| title_sort | il 38 alleviates inflammation in sepsis in mice by inhibiting macrophage apoptosis and activation of the nlrp3 inflammasome |
| url | http://dx.doi.org/10.1155/2021/6370911 |
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