OBJECTIVES: Treatment with anti-TNF agents is well established in psoriatic arthritis (PsA). Anti-TNF agents are capable of modulating complement activity in vitro but there are no data on the in vivo effect. Anti-TNF have high costs and potential risks, thus, there is an urgent need for accurate predictors of response. ...

Tumor necrosis factor (TNF)-α is a pro-inflammatory cytokine associated with psoriasis pathogenesis. Anti-TNF-α therapies are effective in psoriasis. A significant weight gain has been reported in patients treated with anti-TNF-α agents. The aim of the present study was to evaluate the body composition changes in psoriatic patients receiving anti-TNF-α therapies ...

Transforming growth factor-beta (TGF-β) plays a central role in the development of fibrosis by stimulating extracellular matrix accumulation, and signals either directly or indirectly through types I, II, and III (TβRI, II, and III) TGF-β receptor complexes. Ginsan, a polysaccharide extracted from Panax ginseng, has multiple immunomodulatory effects. Here, we ...

Background  There is a granulomatous variant which is recognized in the rosacea spectrum. However, the pathogenesis of granuloma formation in rosacea has not been clearly demonstrated. Matrix metalloproteinases (MMPs) are required for recruitment of inflammatory cells and for tissue remodelling, making way for the development of well-organized granuloma. Objective  The ...

Cleft palate, a malformation of the secondary palate development, is one of the most common human congenital birth defects. Palate formation is a complex process resulting in the separation of the oral and nasal cavities that involves multiple events, including palatal growth, elevation, and fusion. Recent findings show that transforming ...

Transforming growth factor-β1 (TGF-β) was first implicated in mammary epithelial development by Daniel and Silberstein in 1987 and in breast cancer cells and hormone resistance by Lippman and colleagues in 1988. TGF-β is critically important for mammary morphogenesis and secretory function through specific regulation of epithelial proliferation, apoptosis, and extracellular ...

Transforming growth factor (TGF)-β is a pleiotropic cytokine with beneficial and detrimental effects posthematopoietic stem-cell transplantation. TGF-β is increased in specific sites postengraftment and can suppress immune responses and maintain peripheral tolerance. Thus, TGF-β may promote allograft acceptance. However, TGF-β is also the central pathogenic cytokine in fibrotic disease and ...

Patients with tuberous sclerosis complex (TSC) develop fibrous tumours in the brain, skin, kidney, heart and lungs due to TSC1/2 mutations. In the skin, patients develop angiofibromas that have vascular and fibrotic components in which transforming growth factor (TGF)-β and matrix metalloproteinase (MMP)-2 are important. To investigate if the TGF-β ...

It is now generally accepted that TGF-β acts as a pro-metastatic factor in advanced human breast cancer. However, it is well documented, that TGF-β is context dependent, and whether the TGF-β pathway switches to promote metastasis during the progression of squamous cell carcinoma (SCC) is unknown. This study examined the ...

The anorectal spasticity in Hirschsprung disease may be caused by the absence of enteric ganglia and/or the presence of hypertrophic nerves. Anorectal manometry of chemically denervated rectums was compared with that of congenital aganglionic rectums that also possessed hypertrophic nerves. Aganglionic and ganglionic littermates were produced from breeding heterozygous lethal-spotted ...

The objective of this paper is to elucidate the factors contributing to the development and regression of trehalose 6,6'-dimycolate (TDM)-induced model of tuberculous granulomatous lesions. MATERIALS AND TREATMENT: BALB/c mice were twice injected i.p. with a 100 μl of w/o/w emulsion (100 μg of TDM, 3.2 μl of Freund's incomplete adjuvant, 3.2 μl of ...

Lymphedema is a complication of cancer treatment occurring in approximately 50% of patients who undergo lymph node resection. Despite its prevalence, the etiology of this disorder remains unknown. In this study, we determined the effect of soft tissue fibrosis on lymphatic function and the role of transforming growth factor (TGF)-β1 ...

The flexor tendon affects postoperative range of motion in the hand. Transforming growth factor-beta (TGF-β) is a key cytokine in the adhesion formation between the flexor tendon and its surrounding fibro-osseous sheath. The purpose of this study was to examine the inhibition of TGF-β-induced collagen-I production in rabbit flexor tendons ...

Foxp3-expressing regulatory T (T reg) cells have been implicated in parasite-driven inhibition of host immunity during chronic infection. We addressed whether parasites can directly induce T reg cells. Foxp3 expression was stimulated in naive Foxp3⁻ T cells in mice infected with the intestinal helminth Heligmosomoides polygyrus. In vitro, parasite-secreted proteins ...

Transforming growth factor-β (TGF-β) has opposing roles in breast cancer progression by acting as a tumor suppressor in the initial phase, but stimulating invasion and metastasis at later stages. In contrast to the mechanisms by which TGF-β induces growth arrest, the pathways that mediate tumor invasion are not well understood. ...

Vascular calcification is a progressive pathology that occurs in many diseases, including atherosclerosis, diabetes, end-stage renal disease and valve disease. This study aimed to investigate whether decorin and transforming growth factor (TGF)-beta signal modulation occurs during differentiation of vascular smooth muscle cells (SMCs). Decorin and osteopontin expression was identified in ...

Aortic aneurysm (AA) is a common health problem with high mortality and no effective drugs. Transforming growth factor-β (TGF-β) superfamily members regulate various cellular processes, and TGF-β signaling has key roles in development, tissue homeostasis, and diseases. Interest in the role of TGF-β signaling in the pathogenesis of AAs has ...

Hepatocellular carcinoma (HCC) results from the cumulative effects of deregulated tumor suppressor genes and oncogenes. The tumor suppressor and oncogenes commonly affected include growth factors, receptors and their downstream signaling pathway components. The overexpression of transforming growth factor alpha (TGF-alpha) and the inhibition of TGF-beta signaling are especially common in ...

The role of transforming growth factor-beta (TGF-beta) in the development of hepatic metastasis from colon cancer is not clearly elucidated. The aim of this study was to determine the role of TGF-beta in the development of such metastasis. Two human colon cancer cell lines were utilized: FET-alpha cells (intact TGF-beta ...

Senescence induction could be used as an effective treatment for hepatocellular carcinoma (HCC). However, major senescence inducers (p53 and p16(Ink4a)) are frequently inactivated in these cancers. We tested whether transforming growth factor-beta (TGF-beta) could serve as a potential senescence inducer in HCC. First, we screened for HCC cell lines with ...

Dirofilaria repens and other Dirofilaria species are widely distributed parasitic nematodes of carnivores, which occasionally are transmitted to men, causing subcutaneous nodules. In humans, it usually occurs only as single male or female filariae without production of microfilariae. The non-productive living or dead Dirofilaria worms in subcutaneous biopsies from 15 ...

The aim of our study was to advance the knowledge about the biological differences in the healing of the anterior cruciate ligament (ACL) versus the medial collateral ligament (MCL). We quantified α-smooth muscle actin (α-SMA) expression and TGF-β receptor I (TGF-βRI) expression in experimentally injured rabbit ligaments (from day 3 ...

A high protein intake is associated with increased glomerular filtration rate (GFR), which has been suggested to be mediated by reduced signaling of the tubuloglomerular feedback (TGF) mechanism. Nitric oxide (NO) has been shown to contribute to high protein-induced glomerular hyperfiltration, but the specific NO synthase (NOS) isoform responsible is ...

Mutations in fibrillin-1 or fibrillin-2, the major structural components of extracellular microfibrils, cause pleiotropic manifestations in Marfan syndrome and congenital contractural arachnodactyly, respectively. We recently found that fibrillin-1 and fibrillin-2 control bone formation by regulating osteoblast differentiation through the differential modulation of endogenous TGFβ and bone morphogenetic protein signals. Here, ...

TGF-beta plays a crucial role in immune regulation. It has been reported that pro-TGF-beta, latency-associated peptide (LAP), latent TGF-beta and/or active TGF-beta (LAP/TGF-beta) is localized on the cell surface of Foxp3(+) regulatory T cells. However, the molecular mechanism(s) of how LAP/TGF-beta is anchored on the cell membrane is unknown. In ...

The pivotal role of TGF-beta in Langerhans cell (LC) development has been previously established in TGF-beta-deficient mice, which lack epidermal LCs. As to whether TGF-beta also governs LC homeostasis and function remains elusive. To assess the role of TGF-beta-mediated control of cutaneous dendritic cells (DCs) in vivo, we generated mice ...

TGF-β and IL-4 were recently shown to selectively upregulate IL-9 production by naïve CD4(+) T cells. We report here that TGF-β interactions with IL-1α, IL-1β, IL-18, and IL-33 have equivalent IL-9-stimulating activities that function even in IL-4-deficient animals. This was observed after in vitro antigenic stimulation of immunized or unprimed ...

Hepatocellular carcinoma often develops in the setting of abnormal hepatocyte growth associated with chronic hepatitis and liver cirrhosis. Transforming growth factor beta (TGF-beta) is a multifunctional cytokine pivotal in the regulation of hepatic cell growth, differentiation, migration, extracellular matrix production, stem cell homeostasis, and hepatocarcinogenesis. However, the mechanisms by which ...

The term metabolic syndrome (MS) refers to a conglomeration of many metabolic disorders. Recent studies suggest that inflammation plays a vital role in MS. There are however no data available on the recently characterized novel T-cell-derived cytokine interleukin (IL)-17 in MS; studies on the anti-inflammatory cytokine transforming growth factor (TGF)-β ...

BACKGROUND: The novel immunosuppressive molecule, CD200, has been reported to induce immunoregulation after interaction with its receptor(s), CD200R(s), in part at least through augmented induction of regulatory T-cell populations. Independent studies have also described increased expression of indoleamine-2,3-dioxygenase after CD200R triggering, whereas others have provided evidence that TGF-beta is important ...

Pulmonary fibrosis is a type of interstitial lung disease that causes progressive scarring in lung tissues. Although there have been many studies on fibrosis, there is no standard treatment for fibrotic disease. Thus, there is an urgent need for the development of effective anti-fibrotic drugs. Transforming growth factor beta (TGF-beta) ...

Cbl-b is an E3 ubiquitin ligase that negatively regulates T cell activation. Cbl-b(-/-) mice develop spontaneous autoimmunity, and Cbl-b dysregulation has been described in both murine and human autoimmune diseases. Although the mechanisms underlying the development of autoimmunity in Cbl-b(-/-) mice are not yet clear, we have reported that Cbl-b(-/-) ...

Th2-biased inflammation with eosinophilia and IgE production is a hallmark of helminth infections. It is pronounced in hyperreactive onchocerciasis patients ('sowda' or 'local form'), who efficiently kill microfilariae resulting in severe dermatitis and lymphadenitis. In contrast, hyporeactive patients ('generalised form') tolerate high microfilarial loads. This is thought to be mediated ...

We have previously reported that transforming growth factor (TGF)-beta in the cerebrospinal fluid (CSF) is involved in the mechanism underlying the regulation of spontaneous motor activity (SMA) by the central nervous system after exercise. However, it remained unclear what physiological condition triggers the activation of TGF-beta. We hypothesized that the ...

Previous studies have found that matrix metalloproteinase-2 (MMP-2) and transforming growth factor-beta (TGF-beta) can be considered as biomarkers and indices of disease progression in several human cancers. In this study, we investigated the plasma levels of MMP-2 and TGF-beta and their correlation in 49 primary cutaneous melanoma and 10 metastatic ...

TGF-beta plays a key role in upregulating matrix production in injury-induced renal fibrosis, but how TGF-beta signaling in distinct compartments of the kidney, such as specific segments of the nephron, affects the response to injury is unknown. In this study, we determined the role of TGF-beta signaling both in development ...

In many hemolytic disorders, such as malaria, the release of free heme has been involved in the triggering of oxidative stress and tissue damage. Patients presenting with severe forms of malaria commonly have impaired regulatory responses. Although intriguing, there is scarce data about the involvement of heme on the regulation ...

The majority of human skeletal dysplasias are caused by dysregulation of growth plate homeostasis. As TGF-beta signaling is a critical determinant of growth plate homeostasis, skeletal dysplasias are often associated with dysregulation of this pathway. The context-dependent action of TFG-beta signaling is tightly controlled by numerous mechanisms at the extracellular ...

TGF-β is one of the main mediators involved in tissue remodeling in the asthmatic lung. This profibrotic cytokine is produced by a number of cells, including macrophages, epithelial cells, fibroblasts, and eosinophils. High expression of TGF-β in patients with asthma was reported by many investigators. However, controversy remains whether the ...

We examined bystander cell death produced in T98G cells by exposure to irradiated cell conditioned medium (ICCM) produced by high-energy 20 MeV electrons at a dose rate of 10 Gy min(-1) and doses up to 20 Gy. ICCM induced a bystander response in T98G glioma cells, reducing recipient cell survival ...

Is transforming growth factor-beta (TGF-beta) required for induction of the transcription factor Foxp3 in developing thymocytes? Ouyang et al. (2010) demonstrate that TGF-beta in the thymus prevents deletion of Foxp3(+) regulatory T cells.

BACKGROUND: Transforming growth factor-beta (TGF-beta) plays a pivotal role in liver fibrosis, because it activates hepatic stellate cells, stimulating extracellular matrix deposition. Cyclooxygenase-2 (COX-2) has been associated with TGF-beta because its inhibition decreases TGF-beta expression and collagen production in some cultured cell types. AIM: The aim of this work was ...

We used cDNA microarray to identify transforming growth factor beta (TGF-beta) responsive target genes during osteoblast development and found that nephronectin (Npnt) is one such gene that is significantly down-regulated. Here we report the role of TGF-beta in regulating Npnt-mediated osteoblast differentiation. We found that the effect of TGF-beta on ...

Transforming growth factor beta 1 (TGF-beta1) modulates male reproductive function. Genetically modified mice overexpressing alpha/beta subunits of hCG (hCG+) show Leydig cell hyperplasia/hypertrophy at prepuberty that disappears as the mice approach adulthood. In this study we analyzed the gene expression of TGF-beta1, its specific receptors, type II (TGF-betaRII) and type ...

Versican/PG-M is a large chondroitin sulfate proteoglycan in the extracellular matrix, which is transiently expressed in mesenchymal condensation areas during tissue morphogenesis. Here, we generated versican conditional knock-out mice Prx1-Cre/Vcan(flox/flox), in which Vcan is pruned out by site-specific Cre recombinase driven by the Prx1 promoter. Although Prx1-Cre/Vcan(flox/flox) mice are viable ...

Interleukin (IL)-17-producing helper T (T(H)17) cells are a distinct T-cell subset characterized by its pathological role in autoimmune diseases. IL-6 and transforming growth factor-beta (TGF-beta) induce T(H)17 development, in which the orphan nuclear receptors, RORgammat and RORalpha, have an indispensable role. However, in the absence of IL-6 and TGF-beta, the ...

Hepatocellular carcinoma (HCC) is a common cause of death from solid organ malignancy worldwide. Extracellular signal-regulated/mitogen-activated protein kinase kinase (MEK) signaling is a critical growth regulatory pathway in HCC. Targeting MEK with a novel small molecule inhibitor, PD0325901, may inhibit HCC tumorigenesis. PD0325901 (0.01-100 nM) inhibited growth and MEK activity ...

Transforming growth factor-beta (TGF-beta) is a key cytokine in immune regulation, cell differentiation, development, wound healing, and tissue remodelling. It mediates immunosuppression in filarial infections facilitating parasite persistence, while attenuating immunopathology, which is induced by migrating microfilariae. Immunosuppression rises with parasite burden, but it remains unknown whether filariae elicit local ...

Transforming growth factor-beta (TGF-beta) is a cytokine known to participate in several processes related to the development of chronic kidney disease (CKD), including tubular degeneration. This is thought to occur mainly through apoptosis and epithelial-to-mesenchymal transition (EMT) of tubule epithelial cells, which give rise to a reduction of the tubular ...

Transforming growth factor (TGF)-beta signalling plays a dichotomous role in tumour progression, acting as a tumour suppressor early and as a pro-metastatic pathway in late-stages. There is accumulating evidence that advanced-stage tumours produce excessive levels of TGF-beta, which acts to promote tumour growth, invasion and colonisation of secondary organs. In ...