Fig 1: Molecular mechanism underlying cholesterol stimulated cytokine release.Modified LDL cholesterol is absorbed into cells via scatter receptors. At high intracellular concentrations of cholesterol, crystals form. In combination with inflammatory stimuli such as lipopolysaccharide, cholesterol crystals activate NLRP3 inflammasome-caspase-1 activity, leading to the release of mature IL-1b and IL-18. The Toll-like family receptors recognize oxidized LDL. Binding of oxidized LDL cholesterol activates inflammatory signaling via MyD88 and NF?B. This results in increased transcription of the inflammatory cytokines IL-6, IL-12, IL-27 and TNFa. HDL cholesterol alters the activity of ATF3 to suppress TLR activated transcription of inflammatory cytokines.
Fig 2: The effect of statin treatment on IL-18BP and IL-27 levels in human subjects.IL-18BP (A) and IL-27 (B) levels were measured by ELISA at baseline and after two weeks of treatment with atorvastatin, pravastatin, or rosuvastatin. No significant differences were noted between statin treatments on IL-18BP or IL-27. Data are presented as box plots. Center lines show the medians; box limits indicate the 25th and 75th percentiles as determined by R software; whiskers extend to minimum and maximum values; crosses represent sample means; bars indicate 90% confidence intervals of the means. n = 11 subjects for IL-18BP, n = 5 subjects for IL-27.
Fig 3: Cellular mechanism of cholesterol induced TH1 lymphocyte differentiation and atherosclerosis.Dendritic cells and monocytes recognize modified and oxidized LDL cholesterol. In monocytes, this results in release of IL-12 and IL-18 that act on T lymphocytes to promote polarization to TH1 lymphocytes, and promote release of interferon-?. HDL cholesterol and recombinant HDL particles containing apolipoprotein A1 (ApoA1) suppress transcription of IL-12. IL-18 binding protein (IL-18BP) absorbs IL-18, modulating TH1 activation and interferon-? release. Interferon-? augments atherosclerosis. Oxidized LDL promotes release of IL-27, which attenuates atherosclerosis.
Fig 4: Correlation of IL-12 p40 and IL-27 with lipoprotein (a).Pearson’s correlation of IL-12 p40 with lipoprotein (a) levels (r2 = -0.12, p < 0.05, A), and IL-27 with lipoprotein (a) levels (r2 = 0.29, p < 0.003, B) in plasma from human subjects. IL-12 p40, IL-27, and lipoprotein (a) data in n = 11 subjects at baseline and after two weeks treatment with atorvastatin, pravastatin, or rosuvastatin. IL-12 p40 was detected in all study samples. Lipoprotein (a) detected in 43 of 44 study samples. IL-27 detected in 34 of 44 study samples.
Supplier Page from Abcam for Human IL-27 ELISA Kit