Biological Activities ofBacteroides forsythusLipoproteins and Their Possible Pathological Roles in Periodontal Disease

Abstract

Bacteroides forsythus is a gram-negative, anaerobic, fusiform bacterium and is considered to be an etiological agent in periodontal disease. A lipoprotein fraction prepared from B. forsythus cells by Triton X-114 phase separation (BfLP) activated human gingival fibroblasts and a human monocytic cell line, THP-1, to induce interleukin-6 production and tumor necrosis factor alpha production. BfLP was found to be capable of inducing nuclear factor-B translocation in human gingival fibroblasts and THP-1 cells. By using Chinese hamster ovary K1 cells transfected with Toll-like receptor genes together with a nuclear factor-B-dependent CD25 reporter plasmid, it was found that signaling by BfLP was mediated by Toll-like receptor 2 but not by CD14 or Toll-like receptor 4. BfLP induced apoptotic cell death in human gingival fibroblasts, KB cells (an oral epithelial cell line), HL-60 cells (a human myeloid leukemia cell line), and THP-1 cells but not in MOLT4 cells (a T-cell leukemia cell line). Caspase-

Tannerella forsythia invasion in oral epithelial cells requires phosphoinositide 3-kinase activation and clathrin-mediated endocytosis

“…Although the identity of these components is currently unknown, an earlier study has demonstrated that T. forsythia S-layer proteins also mediate attachment to and invasion of KB epithelial cells (Sabet et al, 2003). Interestingly, T. forsythia whole cells and their components have been shown to activate the pattern recognition receptor Toll-like receptor (TLR)2 (Hasebe et al, 2004;Kikkert et al, 2007;Onishi et al, 2008), and PI3K is also a downstream target of TLR2 activation. Thus, the contribution of BspA in invasion and host cell signalling in the context of the bacterial whole cell could not be discerned in this study.…”

Protease-Activated Receptor 2 Mediates Human Beta-Defensin 2 and CC Chemokine Ligand 20 mRNA Expression in Response to Proteases Secreted byPorphyromonas gingivalis

“…Epithelial cell recognition of bacteria and the distinction between commensal and pathogenic bacteria are important processes that occur in the gingival epithelium. It is widely accepted that cells utilize pattern recognition receptors to identify bacteria in their environment (19,51), but in addition, some pathogens, such as Porphyromonas gingivalis, secrete proteases that are recognized by cells via the family of protease-activated receptors (41). Recently, it has been shown that protease-activated receptor 2 (PAR-2) is involved in inflammatory processes in several tissues (24,25,60).…”

The Microbial Aetiology of Periodontal Diseases

“…Adhesion and colonisation Haemagglutinin S-layer Leucin rich proteins BspA Glucosidases Murakami et al 2002Sabet et al, 2003Sakakibara et al, 2007Sharma et al, 1998 Impairment of host defences Proteolytic enzymes corrupt host immunity Surface lipoproteins induce apoptosis Holt & Bramanti 1991Hasebe et al, 2004 Tissue invasion / bone resorption Trypsin-like protease -D-glucosidase and N-acetyl--glucosaminidase PrtH proteinase (forsythe detachment factor) Methylglyoxal product Grenier, 1995Hughes et al, 2003Maiden et al, 2004Saito et al, 1997 …”

“…Oppa, a T. denticola lipoprotein has been proposed to act as an adhesin for the purpose of covering the surface of T. denticola with host proteins in order to avoid, or at least delay, immune recognition (Dashper et al, 2011), while surface proteins of T. forsythia activate host cells to release pro-inflammatory cytokines and induce cellular apoptosis (Hasebe et al, 2004).…”