To elucidate the respective roles of DNA polymorphisms in genes that encode inflammatory markers (such as IL-10, IL-6 and TNF-alpha) and other factors that may affect the development of atherosclerosis (such as apolipoprotein E, transforming growth factor and fetuin-A), sufficiently powered studies are needed in which genotype, the protein product and the specific phenotype all are analysed in relation to outcome.
Marked anti-atheromatous effects of the anti-inflammatory cytokine interleukin-10 (IL-10) were observed in several lipid-driven animal models of arteriosclerosis.
These results may be due to the pleiotropic effects of the cytokines and/or differences in haplotype combination that should be investigated to elucidate the role of TGF-beta1 and IL-10 polymorphisms in atherosclerosis.
To better clarify the role of CD14 in atherosclerosis, we typed CD14 C-260T polymorphism in old Italian (Central of Italy) atherosclerotic patients with carotid stenosis related to lipid assessment, inflammation (soluble CD14, IL-6 serum levels) and IL-6, TNF-alpha, IL-10, Metallothioneins (MT) gene expressions in carotid plaques.
As a part of the Cardiovascular Risk in Young Finns Study, we determined carotid artery compliance (CAC), stiffness index (SI) and Young's elastic modulus (YEM), intima media thickness (IMT), IL10 genotype and atherosclerosis risk parameters for 2260 subjects aged 24-39 years.
In support of a causal role for col(V) autoimmunity in the pathogenesis of atherosclerosis, col(V) sensitization of ApoE(-/-) mice on a regular chow diet overcame IL-10-mediated inhibition of col(V) autoimmunity, leading to increased atherosclerotic burden in these mice and local accumulation of IL-17-producing cells, particularly in the col(V)-rich adventitia subjacent to the atheromas.
The expression of atherosclerosis-related genes was assayed by quantitative real-time PCR, and the production of granulocyte-macrophage colony-stimulating factor, monocyte chemotactic protein-1, interleukin (IL)-1β, IL-10 and IL-12 proteins was determined using ELISA.
Our data identify a novel role for FoxO1 in regulating IL-10 secretion during classic activation and highlight the potential for therapeutic interventions for chronic inflammatory conditions, such as atherosclerosis, diabetes, inflammatory bowel disease, and arthritis.
Atorvastatin treatment increased the percentage and inhibitory ability of nTregs, decreased serum IFN-γ and hsCRP levels, and decreased IL-10 and TGF-β1 levels, as compared with the non-atorvastatin group.Our findings suggest that nTregs play an atheroprotective role in atherosclerosis.
Furthermore, we observed the serum concentrations of HMGB1, IL-17A, and IL-23 were significantly higher in the AS group than in the NCA group (P＜0.01, respectively), whereas the concentrations of serum IL-10 and TGF-β1 were significantly lower in the AS group than in the NCA group (P＜0.01, respectively).
Supporting these observations, ApoE-/- mice that were deficient in IL-10 (IL10-/- ApoE-/- double knockout) failed to show reduced atherosclerosis in 10% oxygen.
We discovered major histocompatibility complex class II-restricted ApoB peptides, which reduce atherosclerosis and induce IL-10-producing CD4<sup>+</sup> T cells and chemokine (C-C motif) receptor 5 expression on regulatory T cells, suggesting that immunization with ApoB peptides inhibits atherosclerosis by inducing anti-inflammatory cytokines.
This study tests a hypothesis that a psychological stress hormone, cortisol, suppresses IL-10 expression in peripheral B cells of patients with atherosclerosis.
Furthermore, a specific deletion of DNGR-1 in CD8α<sup>+</sup> DCs significantly increases IL-10 expression, reduces macrophage and T-cell contents within the lesions, and limits the development of atherosclerosis.
Due to the demonstrated protective function of Breg in different inflammatory diseases mainly through interleukin-10 (IL-10) production, the knowledge of their participation in atherosclerosis immunopathology would be very valuable.
Myeloid protein tyrosine phosphatase 1B (PTP1B) deficiency protects against atherosclerotic plaque formation in the ApoE<sup>-/-</sup> mouse model of atherosclerosis with alterations in IL10/AMPKα pathway.