| First Author | Carballo E | Year | 1998 |
| Journal | Science | Volume | 281 |
| Issue | 5379 | Pages | 1001-5 |
| PubMed ID | 9703499 | Mgi Jnum | J:233592 |
| Mgi Id | MGI:5784999 | Doi | 10.1126/science.281.5379.1001 |
| Citation | Carballo E, et al. (1998) Feedback inhibition of macrophage tumor necrosis factor-alpha production by tristetraprolin. Science 281(5379):1001-5 |
| abstractText | Tumor necrosis factor-alpha (TNF-alpha) is a major mediator of both acute and chronic inflammatory responses in many diseases. Tristetraprolin (TTP), the prototype of a class of Cys-Cys-Cys-His (CCCH) zinc finger proteins, inhibited TNF-alpha production from macrophages by destabilizing its messenger RNA. This effect appeared to result from direct TTP binding to the AU-rich element of the TNF-alpha messenger RNA. TTP is a cytosolic protein in these cells, and its biosynthesis was induced by the same agents that stimulate TNF-alpha production, including TNF-alpha itself. These findings identify TTP as a component of a negative feedback loop that interferes with TNF-alpha production by destabilizing its messenger RNA. This pathway represents a potential target for anti-TNF-alpha therapies. |
