| First Author | Cullinan EB | Year | 1998 |
| Journal | J Immunol | Volume | 161 |
| Issue | 10 | Pages | 5614-20 |
| PubMed ID | 9820540 | Mgi Jnum | J:68065 |
| Mgi Id | MGI:1931998 | Doi | 10.4049/jimmunol.161.10.5614 |
| Citation | Cullinan EB, et al. (1998) IL-1 receptor accessory protein is an essential component of the IL-1 receptor. J Immunol 161(10):5614-20 |
| abstractText | The recently described IL-1R accessory protein (IL-1R AcP) interacts with IL-1beta and the IL-1 type-IR (IL-1RI), but an essential requirement for IL-1R AcP in IL-1 signaling in vitro has not been established and its role in vivo has not been examined. In this study, IL-1R AcP-deficient mice and fibroblasts were produced and characterized. All IL-1 agonists bound to IL-1R AcP-deficient cells through the type I IL-1R, but failed to activate gene expression through either the nuclear factor-kappaB or AP-1-dependent signaling pathways. Absence of IL-1R AcP differentially affected the affinity for IL-1 ligands. IL-1R AcP-deficient fibroblasts bound murine IL-1alpha and human IL-1R antagonist protein (IL-1Ra) with only moderately reduced affinity when compared with wild-type cells, whereas murine IL-1beta affinity was reduced by 70-fold. IL-1 also failed to produce a biologic response in vivo in IL-1R AcP-deficient mice. These data demonstrate that a type I IL-1R/IL-1R AcP complex is required for signaling by all IL-1 agonists and for high affinity binding by IL-1beta. Finally, IL-1R AcP is an essential signal transducing component of the functional IL-1R and should represent a novel target for blocking IL-1 function in human disease. |
