Tannerella forsythia is a major periodontal pathogen, and T. forsythia GroEL is a molecular chaperone homologous to human heat-shock protein 60. Interleukin-17 (IL-17) has been implicated in the pathogenesis of periodontitis and several systemic diseases. This study investigated the potential of T. forsythia GroEL to induce inflammatory bone resorption and examined the cooperative effect of IL-17 and T. forsythia GroEL on inflammatory responses. Human gingival fibroblasts (HGFs) and periodontal ligament (PDL) fibroblasts were stimulated with T. forsythia GroEL and/or IL-17. Gene expression of IL-6, IL-8, and cyclooxygenase-2 (COX-2) and concentrations of IL-6, IL-8, and prostaglandin E (PGE ) were measured by real-time reverse transcription polymerase chain reaction and enzyme-linked immunosorbent assays, respectively. After stimulation of MG63 cells with T. forsythia GroEL and/or IL-17, gene expression of osteoprotegerin (OPG) was examined. After subcutaneous injection of T. forsythia GroEL and/or IL-17 above the calvaria of BALB/c mice, calvarial bone resorption was assessed by micro-computed tomography and histological examination. Tannerella forsythia GroEL induced IL-6 and IL-8 production in HGFs and PDL cells, and IL-17 further promoted IL-6 and IL-8 production. Both T. forsythia GroEL and IL-17 synergistically increased PGE production and inhibited OPG gene expression. Calvarial bone resorption was induced by T. forsythia GroEL injection, and simultaneous injection of T. forsythia GroEL and IL-17 further increased bone resorption. These results suggest that T. forsythia GroEL is a novel virulence factor that can contribute to inflammatory bone resorption caused by T. forsythia and synergizes with IL-17 to exacerbate inflammation and bone resorption.

Platelets play an important role in the regulation of vascular integrity and haemostasis. However, a massive activation and aggregation of platelets can lead to the formation of an arterial thrombus at the site of an atherosclerotic lesion, subsequently increasing the prevalence of ischaemic diseases. 1 Platelet-mediated inflammatory responses are due to highly potent platelet-derived cytokines and the pleiotropic effect on immune cells, which produce a side effect, namely systemic inflammation. 2 Thus, platelet stimulation and activation are known to contribute to inflammation and vascular injury, as well as the initiation of clot formation. This pathophysiological role of platelets reveals the importance of antiplatelet agents as crucial targets in the antiplatelet therapeutic strategy for patients with cardiovascular disorder.Clopidogrel is an oral antiplatelet agent that hinders blood clots by inhibiting the P2Y2 receptor-induced platelet aggregation.Clopidogrel has been proposed to possess pleiotropic biological AbstractAntiplatelet drugs are conventionally used as treatments because of their anti-coagulation functions. However, their pleiotropic effects are of great significance to the treatment of ischaemic cardiovascular diseases. Many studies have reported that an excessive amount of inflammation driven by tumour necrosis factor (TNF) is closely related to the prevalence of atherosclerosis. As the drug selection criteria and evaluation methods related to the anti-TNF activity of antiplatelet drugs remain limited, our investigation of these drugs should prove beneficial. In this study, we compared the anti-TNF activity of three antiplatelet agents, namely clopidogrel, sarpogrelate, and cilostazol, using the TNF-induced inflammatory mouse model. After the oral administration of these drugs, acute inflammation was induced via injection of lipopolysaccharide (LPS) or D-galactosamine (D-gal) and TNF. Serum TNF levels, and the mRNA and protein expression levels of TNF in mouse heart tissue, macrophage accumulation in aortic lesions, and mouse survival were analysed to compare the anti-TNF effects of the three antiplatelet agents. Of the three antiplatelet agents, cilostazol significantly reduced the different levels under the most effective observation. In addition, cilostazol was found to attenuate the TNF-stimulated phosphorylation of mitogen-activated protein kinase (MAPK) and nuclear factor kappa-light-chainenhancer of activated B cell (NF-κB) p65 in the aortic vascular smooth muscle cell line, MOVAS-1 and the D-gal plus TNF-challenged heart tissue of mouse. Therefore, cilostazol is the most ideal of the three antiplatelet drugs for the treatment of TNFmediated inflammatory disorders. K E Y W O R D S