| First Author | VanDeusen JB | Year | 2006 |
| Journal | Eur J Immunol | Volume | 36 |
| Issue | 3 | Pages | 623-30 |
| PubMed ID | 16482512 | Mgi Jnum | J:114830 |
| Mgi Id | MGI:3690208 | Doi | 10.1002/eji.200535241 |
| Citation | VanDeusen JB, et al. (2006) STAT-1-mediated repression of monocyte interleukin-10 gene expression in vivo. Eur J Immunol 36(3):623-30 |
| abstractText | There have been substantial advances in understanding the events that regulate gene expression at the cellular and molecular level; however, there has been limited progress integrating this information to understand how biological systems function in vivo. For example, the anti-inflammatory cytokine IL-10 is thought to down-regulate the effects of the pro-inflammatory cytokine IFN-gamma on monocyte activation following LPS stimulation. However, the often-postulated reciprocal regulation of IL-10 gene expression by IFN-gamma has not been studied in vivo. Here we demonstrate that the regulation of IL-10 gene expression has at least two phases following challenge with LPS or a gram-negative organism. In C57BL/6 mice, early IL-10 induction occurs independently of STAT-1, while a delayed active repression of IL-10 gene expression is critically dependent on STAT-1, but only partially dependent upon IFN-alpha/beta and IFN-gamma. This in vivo IL-10 production comes from blood monocytes, but not tissue macrophages, and cannot be reproduced in vitro. This study provides new insights into the regulation of IL-10 following challenge with a gram-negative organism, and highlights the importance of studying these cytokine regulatory pathways in vivo. |
