Nevertheless, numerous studies have reported macrophage-IFN- responses, and this may occur after treatment with IL-12 and IL-18 (Gerdes and -CL binding TLRVYK on 2-glycoprotein-1 associated with oxLDL, as well as sequences homologous to TLRVYK on and and are potent immunogens, and 10 and 100 g/mL of specific serum IgG are typically induced in infected persons, most of which is the DC-pro-inflammatory cytokine-associated IgG2. atherosclerosis-associated indicators of vascular inflammation, and these markers are elevated in the subset of AgP patients with high -CL. We reason that periodontitis patients with elevated antibodies reactive with oxLDL could be a subgroup at high risk for cardiovascular sequelae. Keywords: aggressive periodontitis, dendritic cells, oxidized low-density lipoprotein, -oxLDL, chronic inflammation, antiphospholipid syndrome Introduction Millions of people are afflicted with chronic inflammatory diseases that involve prolonged suffering, economic loss, and, in some cases, premature death. The results reviewed here derive from studies of periodontal disease, but the mechanisms implicated may apply in atherosclerosis, arthritis, inflammatory bowel disease, and a host of autoimmune disorders, including antiphospholipid syndrome (APS). APS is caused by auto-antibodies produced against 2 glycoprotein I (-CL), and this antibody is of special interest, given that it reacts with oxidized low-density lipoproteins (ox LDL) as well as and (Kebschull and (Wang and in AgP are largely of the IgG2 subclass (Lu serotype b at about 100 g/mL about 10 g/mL for the typically more abundant IgG1 (Wilson and Hamilton, 1992; Lu serotype-specific antigens K1 through K6 (Califano in culture exhibit elevated IgG2 responses but only if DCs are present (Kikuchi and are dominated by IgG2Lu responsesZhang macrophagesMonocyte maturation in AgP is skewed toward dendritic cellsBarbour is a potent inducer of DC-IL-12, whereas IL-10 is the dominant SBI-425 macrophage product under the same conditions (Kikuchi will induce potent DC-IL-12 responses in the presence of IFN-, which also enhances specific IgG2 recall responses (Tanaka contains PC (Tomasz, 1967), and that protective immune responses against murine infection may be mediated SBI-425 by naturally occurring IgM -PC (McNamara also contain PC (Weiser capsular polysaccharide to induce high levels of IgM -PC results in diminished atheroma formation, due to the ability of this antibody to block access of LDL to macrophage scavenger and LDL receptors (Binder are capable of invading human endothelial cells the PAF receptor, demonstrating a potential route of access to the systemic circulation for oral-bacteria-bearing PC (Schenkein molecular mimicry (Blank (TLRIYT), (TLALYK), and (SIRVYK). In addition, other SBI-425 oral organisms may have homologous sequences and contribute to -CL responses. Wang and co-workers (Wang induces antibodies that mimic 2GPI. Additionally, this group has demonstrated a strong association between -CL and periodontitis in individuals with the thrombotic Buergers disease (Chen = 0.93elevated14261.626.6?sVCAM-1normal76661.125.0= 0.91elevated14654.258.3?sE-selectinnormal7664.43.3= 0.49elevated1470.17.6Individuals with CP?sICAM-1normal74280.616.8= 0.41elevated26253.128.3?sVCAM-1normal74676.822.5= 0.62elevated26698.938.0?sE-selectinnormal7477.84.6= 0.98elevated2677.67.80Individuals with GAgP?sICAM-1normal66280.915.4= 0.03elevated24343.825.5?sVCAM-1normal66610.633.62= 0.005elevated24800.155.7?sE-selectinnormal6663.34.0= 0.0002elevated2494.26.7 Open in a separate window This Table is from Schenkein and would induce -CL and that -CL antibodies from immune animals would induce adverse pregnancy outcomes similar to those described by Blank and colleagues (Blank induced antibodies that recognized the cardiolipin/2GPI complex in immunoassays. Furthermore, LECT1 these antibodies induced fetal involution and fetal growth restriction in a mouse model, confirming the findings from Blank (Schenkein (Fig. 1B), although alone was adequate to stimulate DC-IL-12. The concentration of oral bacteria in blood was likely low, and the dose of used was 10,000 cells to model a number that might be obtained in the blood culture from a periodontally healthy individual were stimulated with was 10,000 cells to model a number that might be obtained in the blood 10 DCs. Note that the optimal response to (Aa) occurred when treated with -CL. This experiment was repeated 3 times, and the cultures were set up in triplicate and used to calculate the standard deviations illustrated. (C) Illustration of the enhanced ability of mmLDL to induce DC-IL-12 and promote NK-cell-IFN- when treated with -PC. The LDL used was freshly isolated, and the designation mmLDL is used to indicate that the only modifications to the LDL were the minimal modifications that would occur as the LDL interacts with immune cells and oxygen in culture. NK cells and DCs were stimulated with mmLDL alone or with -PC-treated mmLDL. The supernatant fluids were collected at 48 hrs, and the IL-10, IL-12, and IFN- levels were determined. Addition of -PC to LDL increased IL-12 levels without significantly altering IL-10 levels, resulting in a higher IL-12/IL-10 ratio that corresponded with elevated IFN- responses. **< 0.01. This experiment was repeated 3 times, and the cultures.