The specific aims are to 1. determine the capacity of two inflammatory mediator molecules, interleukin-1 (IL-1) and platelet derived growth factor (PDGF), to alter synthesis of glycosaminoglycans (GAGs) and proteoglycans (PGs) in culture by fibroblasts derived from normal oral mucosa, oral mucosal wound granulation tissue, and mature oral mucosal scar tissues; 2. determine whether fibroblasts derived from wounded and non-wounded tissues are equally responsive to the designated mediators in terms of cellular proliferation and GAG/PG synthesis; and 3. determine if the GAGs or PGs whose synthesis is induced by mediator molecules subsequently exert direct influences on fibroblasts to perpetuate altered synthesis even after exposure to the mediator has ended. Excessive scarring of oral and perioral tissues results from altered matrix metabolism and is a major clinical problem since normal functioning of mucosal structures depends upon their pliability, resilience, barrier function, and absence of strictures; scarring impedes mastication, deglutition, nutrition, respiration, speech and appearance. Fibroblastic lines will be derived from biopsies of normal (uninjured) mucosa as well as from reparative tissues harvested at intervals from buccal mucosal wounds in New Zealand white rabbits. Type I cultures will be exposed to various concentrations of IL-1 or PDGF and then will be assayed for 1. rate of cellular proliferation, 2. GAG composition and synthetic rate and 3. PG protein core composition and synthetic rate. Selected cultures will be assayed for production of endogenous IL-1, endoglycosidases and proteinases. After mediator-induced alterations in GAG/PG production are known, the GAG/PG isolated from Type I cultures will be introduced to a second set of identical cultures (Type II) which have not been exposed previously to mediator molecules. Type II cultures will then be assayed to establish whether the GAG/PG whose synthesis is induced by mediators can exert direct influences on fibroblasts to perpetuate altered matrix synthesis in the absence of mediator.
