| First Author | Weaver A | Year | 2005 |
| Journal | FASEB J | Volume | 19 |
| Issue | 12 | Pages | 1668-70 |
| PubMed ID | 16081501 | Mgi Jnum | J:102657 |
| Mgi Id | MGI:3607881 | Doi | 10.1096/fj.04-2030fje |
| Citation | Weaver A, et al. (2005) An elevated matrix metalloproteinase (MMP) in an animal model of multiple sclerosis is protective by affecting Th1/Th2 polarization. FASEB J 19(12):1668-70 |
| abstractText | Inflammation in multiple sclerosis and its animal model, experimental autoimmune encephalomyelitis (EAE), is manifested by changes in matrix metalloproteinase (MMP) expression and in the ratio of T helper (Th) 1 and 2 effector cytokines. Here, we provide a comprehensive documentation of MMPs in EAE and report that of all the MMPs that could be measured at peak disease in spinal cord tissue, MMP-12 was the most highly up-regulated. In contrast to previously published findings of MMPs in EAE, this increase in MMP-12 expression was associated with protection, as MMP-12 null mice had significantly worse maximum severity and EAE disease burden compared with wild-type (WT) controls. When spleen and lymph node cells were removed from EAE-afflicted WT and MMP-12 null mice at the same disease score before divergence of disease and restimulated in vitro, the MMP-12 null cells had significantly higher Th1 to Th2 cytokine ratio. Measurements of the transcriptional regulators of T cell polarization revealed that MMP-12 null cells had increased T-bet and reduced GATA-3 expression, a condition that favors a Th1 bias. These results emphasize that specific MMPs can have beneficial roles in inflammation, and they implicate MMPs in T effector polarization for the first time. |
