Changes in DNA methylation induced by multi-walled carbon nanotube exposure in the workplace

This study was designed to assess the epigenetic alterations in blood cells, induced by occupational exposure to multi-wall carbon nanotubes (MWCNT). The study population comprised of MWCNT-exposed workers (n=24) and unexposed controls (n=43) from the same workplace. We measured global DNA methylation/hydroxymethylation levels on the 5th...

Network-based integration of molecular and physiological data elucidates regulatory mechanisms underlying adaptation to high-fat diet

Health is influenced by interplay of molecular, physiological and environmental factors. To effectively maintain health and prevent disease, health-relevant relations need to be understood at multiple levels of biological complexity. Network-based methods provide a powerful platform for integration and mining of data and knowledge characterizing...

Elevated expression levels of lysyl oxidases protect against aortic aneurysm progression in Marfan syndrome

Patients with Marfan syndrome (MFS) are at high risk of life-threatening aortic dissections. The condition is caused by mutations in the gene encoding fibrillin-1, an essential component in the formation of elastic fibers. While experimental findings in animal models of the disease have shown the involvement of transforming growth factor-β (TGF...

Synovial inflammation, immune cells and their cytokines in osteoarthritis: A review

Objective: Although osteoarthritis (OA) is considered a non-inflammatory condition, it is widely accepted that synovial inflammation is a feature of OA. However, the role of immune cells and their cytokines in OA is largely unknown. This narrative systematic review summarizes the knowledge of inflammatory properties, immune cells and their...

αB-crystallin is a target for adaptive immune responses and a trigger of innate responses in preactive multiple sclerosis lesions

We present the first comparative analysis of serum immunoglobulinG reactivity profiles against the full spectrum of human myelin-associated proteins in multiple sclerosis patients and healthy control subjects. In both groups, serum antibodies display a consistent and prominent reaction to αB-crystallin (CRYAB) versus other myelin proteins. As an...

TGFbeta affects collagen cross-linking independent of chondrocyte phenotype but strongly depending on physical environment

Transforming growth factor beta (TGFbeta) is often used in cartilage tissue engineering to increase matrix formation by cells with various phenotypes. However, adverse effects of TGFbeta, such as extensive cross-linking in cultured fibroblasts, have also been reported. Our goal was to study effects of TGFbeta on collagen cross-linking and...

Initiating mechanisms of food allergy: Oral tolerance versus allergic sensitization

Immediately after birth the mucosa of the gastrointestinal tract, which represents the greatest body surface area exposed to the outside environment, is confronted with a large variety of foreign antigens. The immune system of the intestine now has to meet the task of discriminating between pathogens and harmless antigens, such as food proteins...

Tissue level, activation and cellular localisation of TGF-beta1 and association with survival in gastric cancer patients

Transforming growth factor-beta1 (TGF-beta1), a tumour suppressing as well as tumour-promoting cytokine, is stored as an extracellular matrix-bound latent complex. We examined TGF-beta1 activation and localisation of TGF-beta1 activity in gastric cancer. Gastric tumours showed increased stromal and epithelial total TGF-beta1 staining by...

Human embryo-conditioned medium stimulates in vitro endometrial angiogenesis

Objective: Successful implantation and placentation depend on the interaction between the endometrium and the embryo. Angiogenesis is crucial at this time. In this article we investigate the direct influence of the human embryo on in vitro endometrial angiogenesis. Design: In vitro study. Setting: Human endometrial microvascular endothelial...

Elevated formation of pyridinoline cross-links by profibrotic cytokines is associated with enhanced lysyl hydroxylase 2b levels

The hallmark of fibrosis is the excessive accumulation of collagen. The deposited collagen contains increased pyridinoline cross-link levels due to an overhydroxylation of lysine residues within the collagen telopeptides. Lysyl hydroxylase 2b (LH2b) is the only lysyl hydroxylase consistently up-regulated in several forms of fibrosis, suggesting...

Involvement of furin-like proprotein convertases in the arterial response to injury

Background: Furin-like proprotein convertases (PCs) are proteolytic activators of proproteins, like membrane type 1-matrix metalloproteinase (MT1-MMP) and transforming growth factor beta (TGF-beta), that are described in the arterial response to injury. However, the involvement of furin-like PCs in the arterial response to injury has not been...

Cytokine and IL-12 receptor mRNA discriminate between different clinical subtypes in multiple sclerosis

Little is known about the involvement of cytokines in the pathogenesis of primary progressive (PP) multiple sclerosis (MS). We evaluated in this cross-sectional study whether IL-18, IL-12p35, IL-12p40, TNF-α, IFN-γ, IL-10, IL-4, TGF-β, IL-12Rβ1, and IL-12Rβ2 mRNA expression in unstimulated white blood cells showed significant differences between...

Species differences in hepatic peroxisome proliferation, cell replication and transforming growth factor-β1 gene expression in the rat, Syrian hamster and guinea pig

The objective of this study was to evaluate species differences in the hepatic effects of three potent rodent peroxisome proliferators, namely methylclofenapate (MCP), ciprofibrate (CIP) and Wy-14,643 (WY), particularly with respect to effects on replicative DNA synthesis and transforming growth factor-β1 (TGF-β1) gene expression. Male Sprague...

Genetic risk factors for autoimmune diseases

In most autoimmune diseases multigenic factors play a significant role in pathogenesis. Progress in identifying these genetic factors, many of which are located outside the major histocompatibility complex, was the subject of a recent meeting. Chemicals/CAS: Interleukin-10, 130068-27-8; Transforming Growth Factor beta; Tumor Necrosis Factor-alpha

Studies on the mechanism of fibrate-inhibited expression of plasminogen activator inhibitor-1 in cultured hepatocytes from cynomolgus monkey

Fibrates are widely used drugs in hyperlipidemic disorders. In addition to lowering serum triglyceride levels, fibrates have also been shown to reduce elevated plasma plasminogen activator inhibitor-1 (PAI-1) levels in vivo. We demonstrate that fibrates suppress PAI-1 synthesis in cultured cynomolgus monkey hepatocytes in a concentration...

Immunomodulator OM 163-induced reversal of tumor-mediated immunosuppression and downregulation of TGF-β1 in vivo

Although PROb colonic tumor cells are immunosuppressive, the immunomodulator OM 163 induced the disappearance of macroscopic peritoneal nodules in 50% of rats bearing a peritoneal carcinomatosis (p.c.) induced by PROb cells. When the p.o. developed, the number of T lymphocytes was low and the expression of interferon (IFN)-γ mRNA in tumor...

Role of transforming growth factor-ß in the preferential induction of T helper cells of type 1 by staphylococcal enterotoxin B

Stimulation of murine CD4+ T cells with staphylococcal enterotoxin B (SEB) results in the preferential development of T helper (Th) 1 cells [i.e. high interferon (IFN)-γ and low interleukin (IL)-4, IL-5 and IL-10]; whereas in response to plate-bound anti-CD3 or anti-T cell receptor-αβ, Th1 as well as Th2 cells develop. In the present study, we...