| First Author | Lou Y | Year | 2014 |
| Journal | PLoS One | Volume | 9 |
| Issue | 5 | Pages | e96508 |
| PubMed ID | 24806446 | Mgi Jnum | J:217365 |
| Mgi Id | MGI:5613796 | Doi | 10.1371/journal.pone.0096508 |
| Citation | Lou Y, et al. (2014) TIPE2 negatively regulates inflammation by switching arginine metabolism from nitric oxide synthase to arginase. PLoS One 9(5):e96508 |
| abstractText | 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 IkappaB degradation and phosphorylation of JNK, p38, and IkappaB 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. |
