| First Author | Lee J | Year | 2012 |
| Journal | J Immunol | Volume | 189 |
| Issue | 4 | Pages | 1928-36 |
| PubMed ID | 22798669 | Mgi Jnum | J:189747 |
| Mgi Id | MGI:5446953 | Doi | 10.4049/jimmunol.1103613 |
| Citation | Lee J, et al. (2012) IL-6 amplifier, NF-kappaB-triggered positive feedback for IL-6 signaling, in grafts is involved in allogeneic rejection responses. J Immunol 189(4):1928-36 |
| abstractText | The IL-6-amplifier first was discovered as a synergistic activation mechanism for NF-kappaB/STAT3 in type 1 collagen(+) cells. This process is marked by the hyperinduction of chemokines and subsequent local inflammation that leads to autoimmune diseases. In this study, we show that IL-6 amplifier activation in grafts plays important roles in allogeneic graft rejection by using a tracheal heterotopic transplantation model that includes bronchiolitis obliterans, a pathological marker for chronic rejection. IL-6, epidermal growth factor, and IFN-gamma all stimulate IL-6 amplifier activation, whereas CCL2, a chemotactic factor for Th1 cells, was one of the amplifier's main targets. Interestingly, IFN-gamma hyperinduced CCL2 in type 1 collagen(+) cells via the IL-6 amplifier at least in vitro. In addition, we detected IL-6, CCL2, phospho-STAT3, and phospho-NF-kappaB in epithelial type 1 collagen(+) cells of allogeneic tracheal grafts. These results show that IL-6 amplifier activation in grafts plays a critical role for graft rejection responses after allogeneic transplantation, including chronic rejection. From these results, we consider whether the IL-6 amplifier in grafts might be a valuable therapeutic target for the prevention of transplant rejection, including chronic rejection. |
