Toll-like receptors, their ligands, and atherosclerosis.

Atherosclerosis is a disease characterized by inflammation in the arterial wall. Atherogenesis is dependent on the innate immune response involving activation of Toll-like receptors (TLRs) and the expression of inflammatory proteins. TLRs, which recognize various pathogen-associated molecular patterns, are expressed in various cell types within the atherosclerotic plaque. Microbial agents are associated with an increased risk of atherosclerosis and this is, in part, due to activation of TLRs. Recently considerable evidence has been provided suggesting that endogenous proteins promote atherosclerosis by binding to TLRs. In this review, we describe the role of TLRs in atherosclerosis with particular emphasis on those atherogenic endogenous proteins that have been implicated as TLR ligands

Antagonists abrogate the effects of Ang II and Ang-(1-7) on SMC proliferation.

<p>Data shown are mean ± SEM of cell numbers at day 4 from 4 experiments, each with triplicate wells per condition.</p

Blockade of the effects of Ang II and Ang-(1-7) on SMC migration by antagonists.

<p>Data shown are mean ± SEM of migration distance from 4 experiments, each with triplicate wells per condition.</p

Ang-(1-7) inhibits Ang II-induced ERK1/2 phosphorylation.

<p>(A) Representative Western blotting results, showing bands for phosphorylated ERK1/2 (p-ERK1/2) and total ERK1/2. (B) Quantification of band intensity of Western blots. Data shown are mean ± SEM of 3 experiments.</p

Ang-(1-7) inhibits the stimulating effect of Ang II on SMC migration.

<p>Data shown are mean ± SEM of migration distance from 4 experiments, each with triplicate wells per condition.</p

Ang-(1-7) inhibits Ang II-induced SMC proliferation.

<p>Data shown are mean ± SEM of cell numbers at day 4 from 4 experiments, each with triplicate wells per condition.</p

Propofol Suppresses Proinflammatory Cytokine Production by Increasing ABCA1 Expression via Mediation by the Long Noncoding RNA LOC286367.

We previously reported that propofol upregulated the expression of ATP-binding cassette transporter subfamily A member 1 (ABCA1) via peroxisome proliferator-activated receptor gamma/liver X receptor in macrophage-derived foam cells. Here, we provide evidence that in addition to inducing ABCA1 expression, propofol represses proinflammatory cytokine production by increasing ABCA1 expression in a LOC286367-dependent manner. Western blot analysis showed that ABCA1 expression was elevated in macrophages by propofol treatment and this effect was markedly reduced by LOC286367 overexpression. Moreover, propofol treatment downregulated the production of the proinflammatory cytokines interleukin-6, tumor necrosis factor, and interferon gamma in lipopolysaccharide-stimulated macrophages by enhancing ABCA1 expression. Notably, propofol achieved this effect in a LOC286367-dependent manner. To the best of our knowledge, this is the first report of the mechanism in which propofol represses proinflammatory cytokine production mediated by ABCA1

Counts and percentages of neutrophil and lymphocyte, and neutrophil-to-lymphocyte ratio, in men and women in different age groups.

<p>Data shown are mean ± standard error of mean in men and women, respectively, in each age group; *indicates p<0.05 comparing men and women in the respective age group.</p

Difference in Leukocyte Composition between Women before and after Menopausal Age, and Distinct Sexual Dimorphism.

There are sex differences in many inflammatory and immune diseases, and the differences tend to diminish after menopause. The underlying reasons are unclear, but sex hormone levels are likely to be an important factor. Blood leukocyte count and composition provide an indicator of the inflammatory and immune status of an individual. We performed a cross-sectional analysis of blood leukocyte data from 46,879 individuals (26,212 men and 20,667 women, aged 18 to 93 years) who underwent a routine health checkup. In women aged around 50 years, neutrophil percentage (NE%) dropped whilst lymphocyte percentage (LY%) rose. Accordingly, women before age 50 had significantly higher NE%, lower LY%, and higher neutrophil-to-lymphocyte ratio (NLR) than women of 51-70 years of age (p = 1.35×10-82, p = 5.32×10-100, and p = 1.25×10-26, respectively). In age groups of 51 years, it was the reverse (p = 1.92×10-15, p = 1.43×10-84, and p = 1.51×10-48, respectively). These results show that blood leukocyte composition differs between women before and after menopausal age, with distinct sexual dimorphism

A Novel Role of Matrix Metalloproteinase-8 in Macrophage Differentiation and Polarization.

Matrix metalloproteinase-8 (MMP8) has been shown to influence various cellular functions. As monocytes and macrophages (Mφ) express MMP8, we investigated if MMP8 played a role in macrophage differentiation and polarization. MMP8 expression was significantly increased during monocyte differentiation into Mφ. Monocyte-derived Mφ from MMP8-deficient mice expressed higher levels of M1-Mφ markers but lower levels of M2-Mφ markers than monocyte-derived Mφ from wild-type mice. Although Mφ from either MMP8-deficient or wild-type mice were inducible by interferon-γ into M1-Mφ, only wild-type Mφ but not MMP8-deficient Mφ could be induced into M2-Mφ by interleukin-4. However, MMP8-deficient Mφ exposed to conditioned culture media of wild-type Mφ developed a M2-Mφ phenotype. Compared with conditioned culture media of wild-type Mφ, conditioned culture media of MMP8-deficient Mφ contained a lower concentration of active transforming growth factor-β (TGF-β), an M2-Mφ inducer. Moreover, evidence also showed that the degradation of the TGF-β sequester, fibromodulin, was modulated by MMP8. The data indicate a previously unknown role of MMP8 in M2-Mφ polarization by cleaving fibromodulin and therefore increasing the bioavailability of the M2-Mφ inducer TGF-β