Pathologic properties of SOD3 variant R213G in the cardiovascular system through the altered neutrophils function.

The SOD3 variant, SOD3R213G, results from substitution of arginine to glycine at amino acid 213 (R213G) in its heparin binding domain (HBD) and is a common genetic variant, reported to be associated with ischemic heart disease. However, little is understood about the role of SOD3R213G in innate immune function, and how it leads to dysfunction of the cardiovascular system. We observed pathologic changes in SOD3R213G transgenic (Tg) mice, including cystic medial degeneration of the aorta, heart inflammation, and increased circulating and organ infiltrating neutrophils.

SOD3 Variant, R213G, Altered SOD3 Function, Leading to ROS-Mediated Inflammation and Damage in Multiple Organs of Premature Aging Mice.

Aims: Among the isoforms of superoxide dismutase, SOD3 is uniquely associated with the extracellular matrix (ECM) by virtue of its heparin-binding domain (HBD). Substitution of arginine by glycine at amino acid 213 (R213G) of its HBD was first identified in patients with heart failure, followed by many studies that focused on the role of this variant (SOD3(R213G)) in ischemic heart disease and cardiovascular disease. However, the biological significance of this mutation in a physiological context is largely unknown.

Loss of extracellular superoxide dismutase induces severe IL-23-mediated skin inflammation in mice.

Psoriasis is a common chronic and complex autoimmune inflammatory skin disorder. The histological characteristics of psoriasis are epidermal hyperplasia, mononuclear leukocyte infiltration into the dermis, and increased angiogenesis. However, the mechanisms involved in the pathogenesis of psoriasis remain unclear.

Role of superoxide dismutase 3 in skin inflammation.

In 1982, a third SOD enzyme was discovered by Marklund and co-workers and named SOD3 on extracellular superoxide dismutase (EC-SOD), as it was shown to be the predominant form in extracellular fluids such as lymph, synovial fluid, and plasma. Many studies have focused on the anti-oxidative effect of SOD3 in the lung and vascular wall where it is highly expressed. Thus, the roles of SOD3 as an anti-oxidative enzyme in ROS-mediated lung inflammation and vascular disease such as ischemia and atherosclerosis, and its mechanism have been extensively studied.

Protein kinase C-θ promotes Th17 differentiation via upregulation of Stat3.

Although protein kinase C-θ (PKC-θ)-deficient mice are resistant to the induction of Th17-dependent experimental autoimmune encephalomyelitis, the function of PKC-θ in Th17 differentiation remains unknown. In this article, we show that purified, naive CD4 PKC-θ(-/-) T cells were defective in Th17 differentiation, whereas Th1 and Th2 differentiation appeared normal. Activation of PKC-θ with PMA promoted Th17 differentiation in wild type (WT) but not PKC-θ(-/-) T cells.

Superoxide dismutase 3 controls adaptive immune responses and contributes to the inhibition of ovalbumin-induced allergic airway inflammation in mice.

Aims: The extracellular superoxide dismutase 3 (SOD3) is an isoform of SOD. Extensive studies have been focused on role of SOD3 as an antioxidant. However, the role of SOD3 in the immune responses that contribute to the inhibition of allergic lung inflammation has not been investigated.

Superoxide dismutase 3 suppresses hyaluronic acid fragments mediated skin inflammation by inhibition of toll-like receptor 4 signaling pathway: superoxide dismutase 3 inhibits reactive oxygen species-induced trafficking of toll-like receptor 4 to lipid rafts.

Aims: Hyaluronic acid (HA) is a component of the extracellular matrix and has been extensively applied for cosmetic, therapeutic, and antiaging purposes. However, HA fragments (HAFs) cause adverse effects. Considering that UV-exposure produces HAF that accumulated on the skin, the role of HAF in skin inflammation and its precise mechanism needs to be clarified, and strategies for the prevention of skin inflammation are necessary.

Regulation of skin inflammation and angiogenesis by EC-SOD via HIF-1α and NF-κB pathways.

Extracellular superoxide dismutase (EC-SOD) is an antioxidant enzyme that breaks down superoxide anion into oxygen and hydrogen peroxide in extracellular spaces and plays key roles in controlling pulmonary and vascular diseases in response to oxidative stresses. We aimed to investigate the role of EC-SOD in angiogenesis and inflammation in chronic inflammatory skin disorders such as psoriasis. Overexpressed EC-SOD reduced expression of angiogenic factors and proinflammatory mediators in hypoxia-induced keratinocytes and in ultraviolet B-irradiated mice, whereas the expression of the antiangiogenic factor tissue inhibitor of metalloproteinase-1 and anti-inflammatory cytokine interleukin-10 were increased.

PKC-θ is a drug target for prevention of T cell-mediated autoimmunity and allograft rejection.

Protein kinase C theta (PKC-θ) is a key kinase in mediating T cell receptor (TCR) signals. PKC-θ activated by T cell receptor (TCR) engagement translocates to immunological synapses and regulates the activation of transcriptional factors NFκB, AP-1, and NFAT. These transcription factors then activate target genes such as IL-2.

Active principle of kimchi, 3-(4'-hydroxyl-3',5'-dimethoxyphenyl)propionic acid, retards fatty streak formation at aortic sinus of apolipoprotein E knockout mice.

We examined the beneficial effects of an active principle in kimchi, 3-(4'-hydroxyl-3',5'-dimethoxyphenyl)propionic acid (HDMPPA), on atherogenesis in apolipoprotein E knockout (apoE KO) mice. ApoE KO mice were fed an atherogenic diet containing 1% cholesterol (control group) with an intraperitoneal injection of chemically synthesized HDMPPA (10 mg/kg/day) (HDMPPA group) for 8 weeks. The aortic sinus atherosclerotic lesion size in the HDMPPA group (n = 10) was significantly smaller (control vs.

Fatty acids modulate Toll-like receptor 4 activation through regulation of receptor dimerization and recruitment into lipid rafts in a reactive oxygen species-dependent manner.

The saturated fatty acids acylated on Lipid A of lipopolysaccharide (LPS) or bacterial lipoproteins play critical roles in ligand recognition and receptor activation for Toll-like Receptor 4 (TLR4) and TLR2. The results from our previous studies demonstrated that saturated and polyunsaturated fatty acids reciprocally modulate the activation of TLR4. However, the underlying mechanism has not been understood.

Lipid-lowering effect of hot water-soluble extracts of Saururus chinensis Bail on rats fed high fat diets.

We evaluated the inhibition of low-density lipoprotein (LDL) oxidation inhibition by a hot water-soluble extract of Saururus chinensis Bail (HWSCB) in vitro and the lipid-lowering effects of HWSCB in rats fed high fat diet (HFD). HFDs were supplemented with 5% HWSCB (HFSCB5 group), 10% HWSCB (HFSCB10 group), or 1% tannic acid (Tannin group). The Tannin group served as a positive control for the study, based on tannic acid's known lipid-lowering effect and water-soluble characteristics.

Role of PKCdelta in IFN-gamma-inducible CIITA gene expression.

The class II transactivator (CIITA) is a key regulatory factor for MHC class II expression. Here, we demonstrate that PKCdelta plays an important role in regulating IFN-gamma-inducible CIITA gene expression in macrophages. Inhibition of PKCdelta by either a PKCdelta inhibitor or a dominant negative (DN) mutant form of PKCdelta led to down-regulation of CIITA expression.

Differential modulation of Nods signaling pathways by fatty acids in human colonic epithelial HCT116 cells.

Nucleotide-binding oligomerization domain-containing proteins (Nods) are intracellular pattern recognition receptors recognizing conserved moieties of bacterial peptidoglycan through their leucine-rich repeats domain. The agonists for Nods activate proinflammatory signaling pathways, including NF-kappaB pathways. The results from our previous studies showed that the activation of TLR4 and TLR2, leucine-rich repeat-containing pattern recognition receptors, were differentially modulated by saturated and n-3 polyunsaturated fatty acids in macrophages and dendritic cells.

Protein kinase C delta is essential to maintain CIITA gene expression in B cells.

Expression of MHC class II genes requires CIITA. Although the transactivation function of CIITA is well characterized, the signaling events that regulate CIITA expression are less understood. In this study, we report that CIITA expression in B cells depends on protein kinase Cdelta (PKCdelta).

ERK and p38 MAPK signaling pathways negatively regulate CIITA gene expression in dendritic cells and macrophages.

The CIITA is a master regulator for MHC class II expression, but the signaling events that control CIITA expression remain poorly understood. In this study, we report that both constitutive and IFN-gamma-inducible expression of CIITA in mouse bone marrow-derived dendritic cells (DC) and macrophages, respectively, are regulated by MAPK signals. In DC, the inhibitory effect of LPS on CIITA expression was prevented by MyD88 deficiency or pharmacological MAPK inhibitors specific for MEK (U0126) and p38 (SB203580), but not JNK (SP600125).

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD)-induced activation of mitogen-activated protein kinase signaling pathway in Jurkat T cells.

The present study was performed to examine mitogen-activated protein kinase associated pathways in mediation of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-induced cell apoptosis in cultured Jurkat T cells. TCDD significantly decreased cell viability in a concentration-dependent manner (P<0.05 at 10-300 nM).

Red pepper attenuates cholesteryl ester transfer protein activity and atherosclerosis in cholesterol-fed rabbits.

Background: The current study was conducted to examine the effect of red pepper supplementation on cholesteryl ester transfer protein (CETP) activity, along with its anti-atherosclerotic effect in cholesterol-fed rabbits.

Methods: Rabbits were fed a 1% cholesterol diet for 12 weeks, including a 1% red pepper powder supplement.

Results: The red pepper supplemented group exhibited significantly lower CETP activity than the control group during the experimental period (P<0.

Cholesteryl ester transfer protein activity and atherogenic parameters in rabbits supplemented with cholesterol and garlic powder.

The current study was conducted to examine the effect of garlic supplementation on CETP activity, along with its anti-atherosclerotic effect in cholesterol-fed rabbits. Rabbits were fed a 1% cholesterol diet for 12 weeks, including a 1% garlic powder supplement. The garlic-supplemented group exhibited significantly lower CETP activity than the control group during the experimental period (P < 0.

Quercetin suppresses proinflammatory cytokines production through MAP kinases andNF-kappaB pathway in lipopolysaccharide-stimulated macrophage.

Quercetin is a flavonoid molecule ubiquitous in nature and functions as an anti-oxidant and anti-inflammatory agent with little toxicity in vivo and in vitro. Dose- and time-dependent effect of quercetin has been investigated on proinflammatory cytokine expression and NO production, focusing on its effects on the MAP kinases and the NF-kappaB signal transduction pathways in LPS-stimulated RAW 264.7 cells by using RT-PCR and immunoblotting.

Differential effects of the optical isomers of KR30031 on cardiotoxicity and on multidrug resistance reversal activity.

The present study was performed to compare the cardiovascular adverse effects of verapamil, KR30031 and their optical isomers, and also to measure their ability to overcome multidrug resistance (MDR). The R-isomer of KR30031 (R-KR30031) was equipotent with the S-isomer of KR30031 (S-KR30031) and 25-fold less potent than the R-isomer of verapamil (R-verapamil) in relaxing the aorta isolated from rat (EC50: 11.8, 10.