| First Author | Mantani PT | Year | 2018 |
| Journal | J Biol Chem | Volume | 293 |
| Issue | 18 | Pages | 6791-6801 |
| PubMed ID | 29572351 | Mgi Jnum | J:264132 |
| Mgi Id | MGI:6189672 | Doi | 10.1074/jbc.RA117.000292 |
| Citation | Mantani PT, et al. (2018) Interleukin-25 (IL-25) has a protective role in atherosclerosis development in the aortic arch in mice. J Biol Chem 293(18):6791-6801 |
| abstractText | Atherosclerosis is a chronic inflammatory disease characterized by the entrapment of apolipoprotein B-containing lipoproteins in the arterial intima, leading to local inflammation. T helper (Th) cell 1-mediated immune responses have been associated with atherosclerosis, and the cytokine interleukin-25 (IL-25 or IL-17E) has been reported to potentially regulate Th1 cell- and Th17 cell-related immune responses. In this study, we evaluated the effects of complete IL-25 deficiency or of a temporal IL-25 blockade on atherosclerosis development in apolipoprotein E-deficient (Apoe(-/-)) mice. Mice deficient in both apolipoprotein E and IL-25 (Apoe(-/-)/IL-25(-/-)) had more Th1 cells in the spleen, along with elevated plasma levels of IL-17 and an increased release of splenic interferon-gamma (INF-gamma). In support of this observation, a 4-week-long treatment of young Apoe(-/-) mice (at 10-14 weeks of age) with an IL-25-blocking antibody increased the release of Th1/Th17-associated cytokines in the spleen. In both mouse models, these findings were associated with increased atherosclerotic plaque formation in the aortic arch. We conclude that complete IL-25 deficiency and a temporal IL-25 blockade during early plaque development aggravate atherosclerosis development in the aortic arch of Apoe(-/-) mice, accompanied by an increase in Th1/Th17-mediated immune responses. Our finding that endogenous IL-25 has an atheroprotective role in the murine aortic arch has potential implications for atherosclerosis development and management in humans. |
