We examined whether functional heterologous complexes between human IL-1RI (hIL-1RI) and murine IL-1R accessory protein (mIL-1RAcP) can be formed, utilizing human fibroblast HEK 293 cells and murine fibroblast C127 cells, nontransfected or stably transfected with hIL-1RI (C127-hIL-1RI), respectively. In non-transfected C127 cells, IL-1beta signalled through the mIL-1RI-mIL-1RAcP complex and activated NFkappaB p50/p65 heterodimers. In C127-hIL-1RI cells, IL-1beta signalled through the hIL-1RI and activated both p65/p65 and p50/p65 NFkappaB complexes, where only the activation of NFkappaB p65/p65 was dependent on mIL-1RAcP. Thus, clearly both homologous and heterologous IL-1RI-IL-1RAcP interactions support NFkappaB translocation, but with differences in signalling pattern.