The pro-inflammatory cytokine IL-1 induced cellular response requires IL-1 receptor complex including IL-1RI and IL-1RAcP. Recently, MyD88 was identified as an adapter molecule in the IL-1 signaling pathway. MyD88 associates with and recruits IRAK to the IL-1 receptor complex in response to IL-1 treatment and dominant negative form of MyD88 attenuates IL-1R-mediated NF-κB activation. MyD88 is also employed as a regulator molecule by IL-18 receptor and human Toll receptor, which are members in the Toll/IL-1R family of receptors. Targeted disruption of the MyD88 gene results in lose of cellular responses to IL-1 and IL-18, and MyD88-deficient mice lack responses to bacterial product LPS that employs Toll-like receptors 2 and 4 (TLR2 and TLR4) as the signaling receptors. MyD88 is a general adapter protein for the Toll/IL-1R family of receptors and plays an important role in the inflammatory response induced by cytokines IL-1 and IL-18 and endotoxin. MyD88 gene is expressed in many tissues.
