| First Author | Suzuki K | Year | 2003 |
| Journal | J Exp Med | Volume | 198 |
| Issue | 11 | Pages | 1717-27 |
| PubMed ID | 14638848 | Mgi Jnum | J:86807 |
| Mgi Id | MGI:2682121 | Doi | 10.1084/jem.20031701 |
| Citation | Suzuki K, et al. (2003) IL-4-Stat6 signaling induces tristetraprolin expression and inhibits TNF-alpha production in mast cells. J Exp Med 198(11):1717-27 |
| abstractText | Increasing evidence has revealed that mast cell-derived tumor necrosis factor alpha (TNF-alpha) plays a critical role in a number of inflammatory responses by recruiting inflammatory leukocytes. In this paper, we investigated the regulatory role of interleukin 4 (IL-4) in TNF-alpha production in mast cells. IL-4 inhibited immunoglobulin E-induced TNF-alpha production and neutrophil recruitment in the peritoneal cavity in wild-type mice but not in signal transducers and activators of transcription 6 (Stat6)-deficient mice. IL-4 also inhibited TNF-alpha production in cultured mast cells by a Stat6-dependent mechanism. IL-4-Stat6 signaling induced TNF-alpha mRNA destabilization in an AU-rich element (ARE)-dependent manner, but did not affect TNF-alpha promoter activity. Furthermore, IL-4 induced the expression of tristetraprolin (TTP), an RNA-binding protein that promotes decay of ARE-containing mRNA, in mast cells by a Stat6-dependent mechanism, and the depletion of TTP expression by RNA interference prevented IL-4-induced down-regulation of TNF-alpha production in mast cells. These results suggest that IL-4-Stat6 signaling induces TTP expression and, thus, destabilizes TNF-alpha mRNA in an ARE-dependent manner. |
