The overall objective of the Research Center in Oral Biology is to investigate the molecular basis of inflammatory tissue destruction and repair. A body of evidence suggests that cytokines and growth factors induced locally in the gingiva in response to microbial colonization mobilize a network of host cell interactions that ultimately results in tissue destruction. This proposal specifically targets the boundary between immune response and tissue destruction. We propose to use a multidisciplinary approach which brings together immunologists, dentists, biochemists and cell biologists and employs state-of-the-art molecular and immunologic methods. The Center is composed of six interrelated research projects and five cores. Project 8 will investigate Bacteroides LPS/Cytokine Regulation In Inflamed Gingival Tissue; Project 4 will investigate Regulation of cellular Inflammatory Responses by IgA; Project 5 will investigate T Cells/Cytokines for B Cell Responses in Oral Disease; Project 3 will study the Molecular Mechanisms of Collagen Degradation by Oral Mucosal Fibroblasts; Project 6 will conduct an Analysis of functional domains in Matrix Metalloproteinases; and Project 7 will examine the Biologic Assembly and Degradation of Fibrillar Structures of the Extracellular Matrix. The Administrative Core will provide administrative support and grants management expertise for Center investigators. The Tissue Procurement core will retrieve human tissue samples for Center research, primarily specimens from the oral mucosa. The Cytokine Core will assist investigators with cytokine analyses at the protein and mRNA levels. The Protein core will provide sequence analysis of proteins and peptides and will synthesize and purify oligopeptides for Center research projects. The DNA Core will provide assistance to investigators in the area of oligonucleotide synthesis and DNA sequencing.