| First Author | Chen H | Year | 2011 |
| Journal | Exp Hematol | Volume | 39 |
| Issue | 5 | Pages | 525-30 |
| PubMed ID | 21320567 | Mgi Jnum | J:177966 |
| Mgi Id | MGI:5296743 | Doi | 10.1016/j.exphem.2011.02.004 |
| Citation | Chen H, et al. (2011) Regulation of MMP-9 expression by the A2b adenosine receptor and its dependency on TNF-alpha signaling. Exp Hematol 39(5):525-30 |
| abstractText | OBJECTIVE: Macrophage- and vascular-derived matrix metalloproteinase (MMP)-9 plays an important role in neointima formation after vascular injury. The A2b adenosine receptor (A2bAR) elevates cyclic adenosine monophosphate and suppresses tumor necrosis factor-alpha (TNF-alpha) levels at baseline and after vascular injury. Considering the influences of TNF-alpha on MMP-9 expression and activity, here we examined the effect of the A2bAR on the expression of MMP-9 and its potential dependency on TNF-alpha. MATERIALS AND METHODS: We applied protein activity and mRNA analyses of MMP-9 in macrophages derived from A2bAR knockout (KO) and TNF-alpha receptor KO mice. We employed guidewire-induced femoral artery injuries on A2bAR KO and control mice and analyzed by immunohistochemistry MMP-9 expression in the neointima area. RESULTS: MMP-9 activity is somewhat less in resident A2bAR KO macrophages compared with wild-type cells. However, MMP-9 is increased in activated macrophages from A2bAR KO when TNF-alpha is further elevated, or in wild-type cells after TNF-alpha treatment. In accordance, A2bAR activation downregulates MMP-9 expression in wild-type macrophages, which is ablated in TNF-alpha receptor KO cells. A greater vascular lesion after femoral artery injury in A2bAR KO mice is associated with elevated TNF-alpha levels and augmented MMP-9, compared to control mice. CONCLUSIONS: Ablation of the A2bAR in activated macrophages increases MMP-9. A2bAR activation reduces MMP-9 expression, which depends on TNF-alpha and could contribute to the protective role of A2bAR in a vascular injury model. |
