INVOLVEMENT OF CD14 ON HUMAN GINGIVAL FIBROBLASTS IN PORPHYROMONAS-GINGIVALIS LIPOPOLYSACCHARIDE-MEDIATED INTERLEUKIN-6 SECRETION

The lipopolysaccharides (LPS) of Porphyromonas gingivalis are implicat ed in the initiation and development of periodontal diseases. However, the mechanisms underlying P. gingivalis LPS-mediated periodontal dest ruction are still unknown. Here, it was found that P. gingivalis LPS a ctivates human gingival fibroblasts (HGF) to release interleukin 6 (IL -6) via CD14, Flow-cytometric analysis showed that HGFs bind to fluore scein-isothiocyanate (FITC)-labelled LPS, and express CD14 on their su rfaces. The binding of FITC-LPS was competitively suppressed by unlabe lled synthetic lipid A as well as by LPS. LPS-induced IL-6 production was inhibited by anti-CD14 monoclonal antibody in a dose-dependent man ner. The binding of FITC-LPS to HGF was abrogated by anti-CD14 monoclo nal antibody. Engagement of LPS initiated the protein tyrosine phospho rylation of several intracellular proteins including extracellular sig nal-regulated kinase (ERK) 1 and 2, and these events were suppressed b y the anti-CD14 monoclonal. These results suggest that CD14 is a cell surface binding site for LPS and is involved in the LPS-mediated activ ation of HGF. (C) 1998 Elsevier Science Ltd. All rights reserved.