THE INTERLEUKIN-1 RECEPTOR ACCESSORY PROTEIN (IL-1RACP) IS ESSENTIAL FOR IL-1-INDUCED ACTIVATION OF INTERLEUKIN-1 RECEPTOR-ASSOCIATED KINASE (IRAK) AND STRESS-ACTIVATED PROTEIN-KINASES (SAP KINASES)

Interleukin-1 (IL-1) is a central mediator of the immune system involv ed in acute and chronic inflammatory responses, Although the sequences of two types of IL-1 receptors are known, the exact molecular events resulting in signal transduction and coupling to downstream signaling elements remain unclear, The recently cloned IL-1 receptor accessory p rotein (IL-1RAcP) has been suggested as a co-receptor molecule for IL- 1RI, supported by the observation that its expression correlates to IL -1 responsiveness, We transfected the EL-4 subline D6/76 with IL-1RAcP cDNA, This cell line is an IL-1 non-responder expressing IL-1RI but l acking constitutive IL-1RAcP expression. The expression of IL-1RAcP in EL-4 D6/76 was sufficient to restore IL-l-induced activation of inter leukin-l receptor-associated kinase and of stress-activated protein ki nases, translocation of the transcription factors NF kappa B and IL-1 NF to the nucleus, and induction of IL-2 mRNA synthesis, These results proved that IL-1RAcP is an indispensible molecule in the IL-1 recepto r signal transduction complex, necessary to link events on the plasma membrane level to downstream signaling pathways, allowing IL-1-depende nt activation of transcription factors and gene expression.