Abstract:
Human mouth has long been recognized as a focal infection and being connected to the systemic health. Periodontal disease is a chronic inflammatory disease caused by Gram-negative bacteria and their products such as Porphyromonas gingivalis. Atherosclerosis, the major cardiovascular disease, is a leading cause of death worldwide. It is a chronic inflammatory disease associated with cholesterol deposition in the arterial walls. The innate immune response of the vascular tissue is known to play important role in atherosclerosis. A hallmark of the atherosclerotic lesion is lipid-laden macrophages or foam cells which are a source of various proinflammatory cytokines including interleukin-1ß (IL-1ß) produced by inflammasome activation. To the best of our knowledge, no previous studies have assessed the role of periodontal infection in atherosclerosis in term of inflammasome activation. In this study, we examined the effects of P. gingivalis LPS and cholesterol crystals on human monocyte derived macrophage in term of NLRP3 inflammasome activation by IL-1ß production and compared the magnitude of inflammasome activation as measured by IL-1ß production between macrophages derived by M-CSF(M2 macrophage) and those derived by GM-CSF(M1 macrophage). The results showed that P. gingivalis LPS and cholesterol crystals induced dose-dependent IL-1ß secretion from both M1 macrophage and M2 macrophage via NLRP3 inflammasome activation when compared with control (p<0.05). No significant differences in IL-1ß production at each concentration of cholesterol crystals were observed between two types of macrophages (p > 0.05). Our results represent the first demonstration that NLRP3 inflammasome activation in human M1 and M2 macrophage via P. gingivalis LPS and cholesterol crystals may be, in part, a possible mechanism of which promote atherosclerosis.
