Search results for " Transcription factor"
showing 10 items of 656 documents
Expression of angiogenic regulators, VEGF and leptin, is regulated by the EGF/PI3K/STAT3 pathway in colorectal cancer cells.
2009
Both leptin and vascular endothelial growth factor (VEGF) are growth and angiogenic cytokines that are upregulated in different types of cancer and have been implicated in neoplastic progression. Here we investigated the molecular mechanism by which leptin and VEGF expression are regulated in colon cancer by epidermal growth factor (EGF). In colon cancer cell line HT-29, EGF induced the binding of signal transducer and activator transcription 3 (STAT3) to STAT3 consensus motifs within the VEGF and leptin promoters and stimulated leptin and VEGF mRNA and protein synthesis. All these EGF effects were significantly blocked when HT-29 cells were treated with an inhibitor of the phosphoinositide…
Fluticasone furoate maintains epithelial homeostasis via leptin/leptin receptor pathway in nasal cells
2014
Leptin is involved in the lung epithelial homeostasis. Its role in the nasal tract is largely unknown. Allergic rhinitis (AR) is induced by the allergen exposure leading to consequential structural abnormalities in the nasal epithelium. Topical corticosteroids are recommended as first-line therapy in AR. Parietaria pollen is one of the most important allergenic sources in the southern Europe. In vitro, in human nasal epithelial cell line RPMI 2650, we aimed to determine whether allergen stimulation acts on leptin/leptin receptor pathway and how fluticasone furoate (FF) influences this pathway. The effects of the major allergen recombinant Par j 1 (rPar j 1), of FF, of leptin, and of TGF-b1 …
Leptin: A pivotal mediator of intestinal inflammation in mice
2002
Abstract Background & Aims: In addition to acting as a regulator of food intake and energy expenditure, leptin can also modulate immune and inflammatory responses. The role of leptin in intestinal inflammation is the focus of the present study. Methods: Acute and chronic colitis were induced in leptin-deficient ob/ob or wild-type (WT) mice using dextran sulfate sodium (DSS) or trinitrobenzene sulfonic acid (TNBS). The severity of colitis was evaluated, and possible mechanisms were studied. Results: Leptin directly stimulates intraepithelial lymphocytes (IELs) and lamina propria mononuclear cells (LPMCs). In the DSS acute model, ob/ob mice exhibited a 72% reduction of colitis severity and sp…
Insulin-dependent leptin expression in breast cancer cells.
2008
Abstract Pathologic conditions associated with hyperinsulinemia, such as obesity, metabolic syndrome, and diabetes, seem to increase the risk of breast cancer. Here, we studied molecular mechanisms by which insulin activates the expression of leptin, an obesity hormone that has been shown to promote breast cancer progression in an autocrine or paracrine way. Using MDA-MB-231 breast cancer cells, we found that (a) insulin stimulated leptin mRNA and protein expression, which was associated with increased activation of the leptin gene promoter; (b) insulin increased nuclear accumulation of transcription factors hypoxia inducible factor (HIF)-1α and Sp1 and their loading on the leptin promoter;…
Effects of PPARγ agonists on the expression of leptin and vascular endothelial growth factor in breast cancer cells.
2013
The obesity hormone leptin has been implicated in breast cancer development. Breast cancer cells express the leptin receptor and are able to synthesize leptin in response to obesity-related stimuli. Furthermore, leptin is a positive regulator of vascular endothelial growth factor (VEGF) and high levels of both proteins are associated with worse prognosis in breast cancer patients. Peroxisome proliferator-activated receptor γ (PPARγ) ligands are therapeutic agents used in patient with Type 2 diabetes and obesity which have recently been studied for their potential anti-tumor effect. Here, we studied if these compounds, ciglitazone and GW1929, can affect the expression of leptin and VEGF in b…
Bisphenol-A impairs insulin action and up-regulates inflammatory pathways in human subcutaneous adipocytes and 3T3-L1 cells.
2013
Current evidence indicates that chemical pollutants may interfere with the homeostatic control of nutrient metabolism, thereby contributing to the increased prevalence of metabolic disorders. Bisphenol-A (BPA) is a lipophilic compound contained in plastic which is considered a candidate for impairing energy and glucose metabolism. We have investigated the impact of low doses of BPA on adipocyte metabolic functions. Human adipocytes derived from subcutaneous adipose tissue and differentiated 3T3-L1 cells were incubated with BPA, in order to evaluate the effect on glucose utilization, insulin sensitivity and cytokine secretion. Treatment with 1 nM BPA significantly inhibited insulin-stimulate…
Cigarette smoke increases BLT2 receptor functions in bronchial epithelial cells: in vitro and ex vivo evidence
2013
Summary Leukotriene B4 (LTB4) is a neutrophil chemotactic molecule with important involvement in the inflammatory responses of chronic obstructive pulmonary disease (COPD). Airway epithelium is emerging as a regulator of innate immune responses to a variety of insults including cigarette smoke, the major risk factor for COPD. In this study we have explored whether cigarette smoke extracts (CSE) or soluble mediators present in distal lung fluid samples (mini-bronchoalveolar lavages) from smokers alter the expression of the LTB4 receptor 2 (BLT2) and peroxisome proliferator-activated receptor-α (PPAR-α) in bronchial epithelial cells. We also evaluated the effects of CSE on the expression of i…
HSP27 controls GATA-1 protein level during erythroid cell differentiation.
2010
AbstractHeat shock protein 27 (HSP27) is a chaperone whose cellular expression increases in response to various stresses and protects the cell either by inhibiting apoptotic cell death or by promoting the ubiquitination and proteasomal degradation of specific proteins. Here, we show that globin transcription factor 1 (GATA-1) is a client protein of HSP27. In 2 models of erythroid differentiation; that is, in the human erythroleukemia cell line, K562 induced to differentiate into erythroid cells on hemin exposure and CD34+ human cells ex vivo driven to erythroid differentiation in liquid culture, depletion of HSP27 provokes an accumulation of GATA-1 and impairs terminal maturation. More spec…
Production of interleukin-13 by human dendritic cells after stimulation with protein allergens is a key factor for induction of T helper 2 cytokines …
2003
Dendritic cells (DC) are able to induce not only T helper 1 (Th1) but also Th2 immune responses after stimulation with allergens. While DC-derived interleukin (IL)-12 and IL-18 are the key factors for the induction of Th1 cells, early signals being involved in Th2 differentiation are less well characterized so far. To analyse such early signals we used an antigen-specific setting with CD4+ T cells from atopic donors stimulated in the presence of autologous mature DC, which were pulsed with different allergen doses. The addition of increasing amounts of allergen during DC maturation with tumour necrosis factor-alpha, IL-1beta and prostaglandin E2 resulted in enhanced secretion of IL-6 and IL…
Adaptive suppression of the ATF4–CHOP branch of the unfolded protein response by toll-like receptor signalling
2009
The endoplasmic reticulum (ER) unfolded protein response (UPR) restores equilibrium to the ER, but prolonged expression of the UPR effector CHOP (GADD153) is cytotoxic. We found that CHOP expression induced by ER stress was suppressed by prior engagement of toll-like receptor (TLR) 3 or 4 through a TRIF-dependent pathway. TLR engagement did not suppress phosphorylation of PERK or eIF-2alpha, which are upstream of CHOP, but phospho-eIF-2alpha failed to promote translation of the CHOP activator ATF4. In mice subjected to systemic ER stress, pretreatment with low dose lipopolysaccharide (LPS), a TLR4 ligand, suppressed CHOP expression and apoptosis in splenic macrophages, renal tubule cells an…