Characterization of Hsc70 interactions regulating LPS stimulated RA W264. 7 cells. The central hypothesis for this Louisiana Biomedical Research Network (LBRN) Start-Up proposal is that comprehensively defining Hsc70 interactions with client and non-client proteins will clarify intricacies in the regulation of lipopolysaccharide (LPS) regulation with toll-like receptor 4 (TLR4) to activate tumor necrosis factor a (TNFa). This signaling pathway is crucial to evoking a robust inflammatory response to bacterial infection but uncontrolled production of TNFa can be extremely hazardous to the host. Substantial evidence supports a contribution by Hsc70 in augmenting LPS-induced TNFa secretion. A fuller understanding of the role of Hsc70 in modulating this critical innate immune response is therefore crucial to being able to completely understand the overwhelming production of TNFa in diseases such as rheumatoid arthritis and sepsis can be addressed.