The treatment of inflammation and bone loss. Inflammatory conditions such as periodontal disease result in both local and systemic immune responses that often lead to deleterious consequences, including bone loss. The primary mediators of these events are inflammatory cytokines, such as interleukin (IL)-17. To date, only one subunit of the IL-17 receptor (IL-17R) has been identified, and it is not clear whether other subunit also participate in the IL-17R signaling complex. Since typical cytokine receptors consist of at least two subunits, we hypothesis that the IL-17R also exists as a multimer. To determine whether the subunits form a homodimer, three approaches will be used, including a chimeric receptor approach, flurescence resonance energy transfer, and biochemical cross-linking. In addition, we propose to delineate specific amino acids of the IL-17R that are critical for binding to IL-17 and mediating a specific signal. This will be done by receptor truncations and site directed mutagenesis. Elucidation of the IL-17R configuration and binding domains has potential therapeutic applications in the treatment of inflammatory diseases such as periodontitis.
