| First Author | Lou Y | Year | 2013 |
| Journal | J Immunol | Volume | 191 |
| Issue | 9 | Pages | 4849-57 |
| PubMed ID | 24081993 | Mgi Jnum | J:206231 |
| Mgi Id | MGI:5548246 | Doi | 10.4049/jimmunol.1300053 |
| Citation | Lou Y, et al. (2013) Enhanced atherosclerosis in TIPE2-deficient mice is associated with increased macrophage responses to oxidized low-density lipoprotein. J Immunol 191(9):4849-57 |
| abstractText | Atherosclerosis has been widely recognized as an inflammatory disease of the arterial wall in which macrophages play a major role. Yet, how macrophage-mediated pathology is regulated during atherosclerosis is poorly understood. TNF-alpha-induced protein 8-like 2 (TIPE2, also known as TNFAIP8L2) is highly expressed in resting macrophages and can negatively regulate inflammation through inhibiting immune receptor signaling. We report in this article that TIPE2 plays a crucial atheroprotective role likely by regulating macrophage responses to oxidized low-density lipoprotein (ox-LDL). TIPE2-deficient macrophages treated with ox-LDL produced more oxidative stress and proinflammatory cytokines, and exhibited heightened activation of the JNK, NF-kappaB, and p38 signaling pathways. As a consequence, TIPE2 deficiency in bone marrow-derived cells exacerbated atherosclerosis development in Ldlr(-/-) mice fed a high-fat diet. Importantly, ox-LDL markedly downregulated TIPE2 mRNA and protein levels in macrophages, suggesting that ox-LDL mediates atherosclerosis by TIPE2 inhibition. These results indicate that TIPE2 is a new inhibitor of atherosclerosis and a potential drug target for treating the disease. |
