TIPE2 negatively regulates inflammation by switching arginine metabolism from nitric oxide synthase to arginase.
TIPE2, the tumor necrosis factor (TNF)-alpha-induced protein 8-like 2 (TNFAIP8L2), plays an essential role in maintaining immune homeostasis. It is highly expressed in macrophages and negatively regulates inflammation through inhibiting Toll-like receptor signaling. In this paper, we utilized RAW264...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2014-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC4013027?pdf=render |
| _version_ | 1828231653184503808 |
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| author | Yunwei Lou Guizhong Zhang Minghong Geng Wenqian Zhang Jian Cui Suxia Liu |
| author_facet | Yunwei Lou Guizhong Zhang Minghong Geng Wenqian Zhang Jian Cui Suxia Liu |
| author_sort | Yunwei Lou |
| collection | DOAJ |
| description | TIPE2, the tumor necrosis factor (TNF)-alpha-induced protein 8-like 2 (TNFAIP8L2), plays an essential role in maintaining immune homeostasis. It is highly expressed in macrophages and negatively regulates inflammation through inhibiting Toll-like receptor signaling. In this paper, we utilized RAW264.7 cells stably transfected with a TIPE2 expression plasmid, as well as TIPE2-deficient macrophages to study the roles of TIPE2 in LPS-induced nitric oxide (NO) and urea production. The results showed that TIPE2-deficiency significantly upregulated the levels of iNOS expression and NO production in LPS-stimulated macrophages, but decreased mRNA levels of arginase I and urea production. However, TIPE2 overexpression in macrophages was capable of downregulating protein levels of LPS-induced iNOS and NO, but generated greater levels of arginase I and urea production. Furthermore, TIPE2-/- mice had higher iNOS protein levels in lung and liver and higher plasma NO concentrations, but lower levels of liver arginase I compared to LPS-treated WT controls. Interestingly, significant increases in IκB degradation and phosphorylation of JNK, p38, and IκB were observed in TIPE2-deficient macrophages following LPS challenge. These results strongly suggest that TIPE2 plays an important role in shifting L-arginase metabolism from production of NO to urea, during host inflammatory response. |
| first_indexed | 2024-04-12T19:07:33Z |
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| id | doaj.art-1f6e87d7ce1f4fa5898ff7339970a2f0 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-12T19:07:33Z |
| publishDate | 2014-01-01 |
| publisher | Public Library of Science (PLoS) |
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| series | PLoS ONE |
| spelling | doaj.art-1f6e87d7ce1f4fa5898ff7339970a2f02022-12-22T03:19:58ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-0195e9650810.1371/journal.pone.0096508TIPE2 negatively regulates inflammation by switching arginine metabolism from nitric oxide synthase to arginase.Yunwei LouGuizhong ZhangMinghong GengWenqian ZhangJian CuiSuxia LiuTIPE2, the tumor necrosis factor (TNF)-alpha-induced protein 8-like 2 (TNFAIP8L2), plays an essential role in maintaining immune homeostasis. It is highly expressed in macrophages and negatively regulates inflammation through inhibiting Toll-like receptor signaling. In this paper, we utilized RAW264.7 cells stably transfected with a TIPE2 expression plasmid, as well as TIPE2-deficient macrophages to study the roles of TIPE2 in LPS-induced nitric oxide (NO) and urea production. The results showed that TIPE2-deficiency significantly upregulated the levels of iNOS expression and NO production in LPS-stimulated macrophages, but decreased mRNA levels of arginase I and urea production. However, TIPE2 overexpression in macrophages was capable of downregulating protein levels of LPS-induced iNOS and NO, but generated greater levels of arginase I and urea production. Furthermore, TIPE2-/- mice had higher iNOS protein levels in lung and liver and higher plasma NO concentrations, but lower levels of liver arginase I compared to LPS-treated WT controls. Interestingly, significant increases in IκB degradation and phosphorylation of JNK, p38, and IκB were observed in TIPE2-deficient macrophages following LPS challenge. These results strongly suggest that TIPE2 plays an important role in shifting L-arginase metabolism from production of NO to urea, during host inflammatory response.http://europepmc.org/articles/PMC4013027?pdf=render |
| spellingShingle | Yunwei Lou Guizhong Zhang Minghong Geng Wenqian Zhang Jian Cui Suxia Liu TIPE2 negatively regulates inflammation by switching arginine metabolism from nitric oxide synthase to arginase. PLoS ONE |
| title | TIPE2 negatively regulates inflammation by switching arginine metabolism from nitric oxide synthase to arginase. |
| title_full | TIPE2 negatively regulates inflammation by switching arginine metabolism from nitric oxide synthase to arginase. |
| title_fullStr | TIPE2 negatively regulates inflammation by switching arginine metabolism from nitric oxide synthase to arginase. |
| title_full_unstemmed | TIPE2 negatively regulates inflammation by switching arginine metabolism from nitric oxide synthase to arginase. |
| title_short | TIPE2 negatively regulates inflammation by switching arginine metabolism from nitric oxide synthase to arginase. |
| title_sort | tipe2 negatively regulates inflammation by switching arginine metabolism from nitric oxide synthase to arginase |
| url | http://europepmc.org/articles/PMC4013027?pdf=render |
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