Intravenous Arginine Administration Benefits CD4<sup>+</sup> T-Cell Homeostasis and Attenuates Liver Inflammation in Mice with Polymicrobial Sepsis
This study investigated the effects of a single dose of arginine (Arg) administration at the beginning of sepsis on CD4<sup>+</sup> T-cell regulation and liver inflammation in C57BL/6J mice. Mice were divided into normal control (NC), sham (SH), sepsis saline (SS), and sepsis Arg (SA) gr...
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MDPI AG
2020-04-01
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| Series: | Nutrients |
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| Online Access: | https://www.mdpi.com/2072-6643/12/4/1047 |
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| author | Chiu-Li Yeh Sharon Angela Tanuseputero Jin-Ming Wu Yi-Ru Tseng Po-Jen Yang Po-Chu Lee Sung-Ling Yeh Ming-Tsan Lin |
| author_facet | Chiu-Li Yeh Sharon Angela Tanuseputero Jin-Ming Wu Yi-Ru Tseng Po-Jen Yang Po-Chu Lee Sung-Ling Yeh Ming-Tsan Lin |
| author_sort | Chiu-Li Yeh |
| collection | DOAJ |
| description | This study investigated the effects of a single dose of arginine (Arg) administration at the beginning of sepsis on CD4<sup>+</sup> T-cell regulation and liver inflammation in C57BL/6J mice. Mice were divided into normal control (NC), sham (SH), sepsis saline (SS), and sepsis Arg (SA) groups. An inducible nitric oxide (NO) synthase (iNOS) inhibitor was administered to additional sepsis groups to evaluate the role of NO during sepsis. Sepsis was induced using cecal ligation and puncture (CLP). The SS and SA groups received saline or Arg (300 mg/kg body weight) via tail vein 1 h after CLP. Mice were euthanized at 12 and 24 h post-CLP. Blood, para-aortic lymph nodes, and liver tissues were collected for further measurement. The findings showed that sepsis resulted in decreases in blood and para-aortic lymph node CD4<sup>+</sup> T-cell percentages, whereas percentages of interleukin (IL)-4- and IL-17-expressing CD4<sup>+</sup> T cells were upregulated. Compared to the SS group, Arg administration resulted in maintained circulating and para-aortic lymph node CD4<sup>+</sup> T cells, an increased Th1/Th2 ratio, and a reduced Th17/Treg ratio post-CLP. In addition, levels of plasma liver injury markers and expression of inflammatory genes in liver decreased. These results suggest that a single dose of Arg administered after CLP increased Arg availability, sustained CD4<sup>+</sup> T-cell populations, elicited more-balanced Th1/Th2/Th17/Treg polarization in the circulation and the para-aortic lymph nodes, and attenuated liver inflammation in sepsis. The favorable effects of Arg were abrogated when an iNOS inhibitor was administered, which indicated that NO may be participated in regulating the homeostasis of Th/Treg cells and subsequent liver inflammation during sepsis. |
| first_indexed | 2024-03-10T20:32:40Z |
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| id | doaj.art-1a856d930e7f44e9bfdd4f56de93af6e |
| institution | Directory Open Access Journal |
| issn | 2072-6643 |
| language | English |
| last_indexed | 2024-03-10T20:32:40Z |
| publishDate | 2020-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Nutrients |
| spelling | doaj.art-1a856d930e7f44e9bfdd4f56de93af6e2023-11-19T21:13:43ZengMDPI AGNutrients2072-66432020-04-01124104710.3390/nu12041047Intravenous Arginine Administration Benefits CD4<sup>+</sup> T-Cell Homeostasis and Attenuates Liver Inflammation in Mice with Polymicrobial SepsisChiu-Li Yeh0Sharon Angela Tanuseputero1Jin-Ming Wu2Yi-Ru Tseng3Po-Jen Yang4Po-Chu Lee5Sung-Ling Yeh6Ming-Tsan Lin7School of Nutrition and Health Sciences, College of Nutrition, Taipei Medical University, Taipei 11031, TaiwanSchool of Nutrition and Health Sciences, College of Nutrition, Taipei Medical University, Taipei 11031, TaiwanDepartment of Surgery, National Taiwan University Hospital and College of Medicine, National Taiwan University, Taipei 10002, TaiwanSchool of Nutrition and Health Sciences, College of Nutrition, Taipei Medical University, Taipei 11031, TaiwanDepartment of Surgery, National Taiwan University Hospital and College of Medicine, National Taiwan University, Taipei 10002, TaiwanDepartment of Surgery, National Taiwan University Hospital and College of Medicine, National Taiwan University, Taipei 10002, TaiwanSchool of Nutrition and Health Sciences, College of Nutrition, Taipei Medical University, Taipei 11031, TaiwanDepartment of Surgery, National Taiwan University Hospital and College of Medicine, National Taiwan University, Taipei 10002, TaiwanThis study investigated the effects of a single dose of arginine (Arg) administration at the beginning of sepsis on CD4<sup>+</sup> T-cell regulation and liver inflammation in C57BL/6J mice. Mice were divided into normal control (NC), sham (SH), sepsis saline (SS), and sepsis Arg (SA) groups. An inducible nitric oxide (NO) synthase (iNOS) inhibitor was administered to additional sepsis groups to evaluate the role of NO during sepsis. Sepsis was induced using cecal ligation and puncture (CLP). The SS and SA groups received saline or Arg (300 mg/kg body weight) via tail vein 1 h after CLP. Mice were euthanized at 12 and 24 h post-CLP. Blood, para-aortic lymph nodes, and liver tissues were collected for further measurement. The findings showed that sepsis resulted in decreases in blood and para-aortic lymph node CD4<sup>+</sup> T-cell percentages, whereas percentages of interleukin (IL)-4- and IL-17-expressing CD4<sup>+</sup> T cells were upregulated. Compared to the SS group, Arg administration resulted in maintained circulating and para-aortic lymph node CD4<sup>+</sup> T cells, an increased Th1/Th2 ratio, and a reduced Th17/Treg ratio post-CLP. In addition, levels of plasma liver injury markers and expression of inflammatory genes in liver decreased. These results suggest that a single dose of Arg administered after CLP increased Arg availability, sustained CD4<sup>+</sup> T-cell populations, elicited more-balanced Th1/Th2/Th17/Treg polarization in the circulation and the para-aortic lymph nodes, and attenuated liver inflammation in sepsis. The favorable effects of Arg were abrogated when an iNOS inhibitor was administered, which indicated that NO may be participated in regulating the homeostasis of Th/Treg cells and subsequent liver inflammation during sepsis.https://www.mdpi.com/2072-6643/12/4/1047argininesepsisnitric oxideT helper cellregulatory T cellliver inflammation |
| spellingShingle | Chiu-Li Yeh Sharon Angela Tanuseputero Jin-Ming Wu Yi-Ru Tseng Po-Jen Yang Po-Chu Lee Sung-Ling Yeh Ming-Tsan Lin Intravenous Arginine Administration Benefits CD4<sup>+</sup> T-Cell Homeostasis and Attenuates Liver Inflammation in Mice with Polymicrobial Sepsis Nutrients arginine sepsis nitric oxide T helper cell regulatory T cell liver inflammation |
| title | Intravenous Arginine Administration Benefits CD4<sup>+</sup> T-Cell Homeostasis and Attenuates Liver Inflammation in Mice with Polymicrobial Sepsis |
| title_full | Intravenous Arginine Administration Benefits CD4<sup>+</sup> T-Cell Homeostasis and Attenuates Liver Inflammation in Mice with Polymicrobial Sepsis |
| title_fullStr | Intravenous Arginine Administration Benefits CD4<sup>+</sup> T-Cell Homeostasis and Attenuates Liver Inflammation in Mice with Polymicrobial Sepsis |
| title_full_unstemmed | Intravenous Arginine Administration Benefits CD4<sup>+</sup> T-Cell Homeostasis and Attenuates Liver Inflammation in Mice with Polymicrobial Sepsis |
| title_short | Intravenous Arginine Administration Benefits CD4<sup>+</sup> T-Cell Homeostasis and Attenuates Liver Inflammation in Mice with Polymicrobial Sepsis |
| title_sort | intravenous arginine administration benefits cd4 sup sup t cell homeostasis and attenuates liver inflammation in mice with polymicrobial sepsis |
| topic | arginine sepsis nitric oxide T helper cell regulatory T cell liver inflammation |
| url | https://www.mdpi.com/2072-6643/12/4/1047 |
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