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Title: Plasminogen activation by fibroblasts from periodontal ligament and gingiva is not directly affected by chemokines in vitro. Author: Sarajlic J, Agis H, Kandler B, Watzek G, Gruber R. Journal: Arch Oral Biol; 2007 Jul; 52(7):663-8. PubMed ID: 17296163. Abstract: OBJECTIVE: Chronic inflammation in periodontal disease is associated with increased plasminogen activation and elevated levels of chemokines. It is unknown whether chemokines can regulate the activation of plasminogen via modulation of plasminogen activators (PA) and the corresponding plasminogen activator inhibitors (PAI) in periodontal tissue. DESIGN: To establish a link between chemokines and activation of plasminogen, human periodontal ligament fibroblasts (PDL) and gingival fibroblasts (GF) were incubated with IL-8, monocyte chemoattractant protein-1, macrophage inflammatory protein-1alpha, and platelet factor-4, either alone or in the presence of the inflammatory mediators TGF-beta and IL-1. The potential of the cell lysates to activate plasminogen was based on kinetic studies with the substrate casein. Casein zymography was performed to determine the molecular sizes of the PA. Total PAI-1 in the cell-conditioned medium was quantified by immunoassay. RESULTS: We report that the chemokines did not affect activation of plasminogen by PDL and GF. Even in the presence of TGF-beta which suppressed, and IL-1 which stimulated plasminogen activation, the chemokines had no direct effect. Inhibition of PA and plasmin, but not of matrix metalloproteinases and cysteine proteinases prevented caseinolysis. The plasminogen activation capacity of the cell lysates was represented by a single band with features of uPA. The immunoassay showed that the release of PAI-1 in PDL and GF remained unaffected by the chemokines, also when stimulated with TGF-beta. CONCLUSIONS: These results suggest that plasminogen activation by PDL and GF is not directly affected by the chemokines even in the presence of the inflammatory mediators TGF-beta and IL-1.[Abstract] [Full Text] [Related] [New Search]