PMID- 17296163 OWN - NLM STAT- MEDLINE DCOM- 20071218 LR - 20121115 IS - 0003-9969 (Print) IS - 0003-9969 (Linking) VI - 52 IP - 7 DP - 2007 Jul TI - Plasminogen activation by fibroblasts from periodontal ligament and gingiva is not directly affected by chemokines in vitro. PG - 663-8 AB - 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. FAU - Sarajlic, Jasna AU - Sarajlic J AD - Department of Oral Surgery, Medical University of Vienna, Vienna, Austria, Wahringerstrasse 25a, A-1090 Vienna, Austria. FAU - Agis, Hermann AU - Agis H FAU - Kandler, Barbara AU - Kandler B FAU - Watzek, Georg AU - Watzek G FAU - Gruber, Reinhard AU - Gruber R LA - eng PT - Journal Article DEP - 20070212 PL - England TA - Arch Oral Biol JT - Archives of oral biology JID - 0116711 RN - 0 (Caseins) RN - 0 (Chemokine CCL2) RN - 0 (Chemokine CCL3) RN - 0 (Chemokines) RN - 0 (Culture Media, Conditioned) RN - 0 (Cysteine Proteinase Inhibitors) RN - 0 (Inflammation Mediators) RN - 0 (Interleukin-1) RN - 0 (Interleukin-8) RN - 0 (Matrix Metalloproteinase Inhibitors) RN - 0 (Plasminogen Inactivators) RN - 0 (Transforming Growth Factor beta) RN - 37270-94-3 (Platelet Factor 4) RN - 9001-91-6 (Plasminogen) RN - EC 3.4.21.- (Plasminogen Activators) RN - EC 3.4.21.73 (Urokinase-Type Plasminogen Activator) SB - IM MH - Caseins/metabolism MH - Cells, Cultured MH - Chemokine CCL2/pharmacology MH - Chemokine CCL3/pharmacology MH - Chemokines/*pharmacology MH - Culture Media, Conditioned MH - Cysteine Proteinase Inhibitors/pharmacology MH - Fibroblasts/drug effects/*metabolism MH - Gingiva/cytology/drug effects/*metabolism MH - Humans MH - Inflammation Mediators/pharmacology MH - Interleukin-1/pharmacology MH - Interleukin-8/pharmacology MH - Matrix Metalloproteinase Inhibitors MH - Periodontal Ligament/cytology/drug effects/*metabolism MH - Plasminogen/drug effects/*metabolism MH - Plasminogen Activators/analysis/drug effects MH - Plasminogen Inactivators/metabolism MH - Platelet Factor 4/pharmacology MH - Transforming Growth Factor beta/pharmacology MH - Urokinase-Type Plasminogen Activator/analysis EDAT- 2007/02/14 09:00 MHDA- 2007/12/19 09:00 CRDT- 2007/02/14 09:00 PHST- 2006/07/28 00:00 [received] PHST- 2006/12/04 00:00 [revised] PHST- 2006/12/18 00:00 [accepted] PHST- 2007/02/14 09:00 [pubmed] PHST- 2007/12/19 09:00 [medline] PHST- 2007/02/14 09:00 [entrez] AID - S0003-9969(07)00022-2 [pii] AID - 10.1016/j.archoralbio.2006.12.020 [doi] PST - ppublish SO - Arch Oral Biol. 2007 Jul;52(7):663-8. doi: 10.1016/j.archoralbio.2006.12.020. Epub 2007 Feb 12.