Search results for "stat3"
showing 10 items of 106 documents
The STAT3 Inhibitor Galiellalactone Reduces IL6-Mediated AR Activity in Benign and Malignant Prostate Models
2018
IL6/STAT3 signaling is associated with endocrine therapy resistance in prostate cancer, but therapies targeting this pathway in prostate cancer were unsuccessful in clinical trials so far. The mechanistic explanation for this phenomenon is currently unclear; however, IL6 has pleiotropic effects on a number of signaling pathways, including the androgen receptor (AR). Therefore, we investigated IL6-mediated AR activation in prostate cancer cell lines and ex vivo primary prostate tissue cultures in order to gain a better understanding on how to inhibit this process for future clinical trials. IL6 significantly increased androgen-dependent AR activity in LNCaP cells but importantly did not infl…
Cancer cells induce immune escape via glycocalyx changes controlled by the telomeric protein TRF2
2019
International audience; Myeloid-derived suppressor cells (MDSCs) are immature myeloid cells with strong immunosuppressive activity that promote tumor growth. In this study, we describe a mechanism by which cancer cells control MDSCs in human cancers by upregulating TRF2, a protein required for telomere stability. Specifically, we showed that the TRF2 upregulation in cancer cells has extratelomeric roles in activating the expression of a network of genes involved in the biosynthesis of heparan sulfate proteoglycan, leading to profound changes in glycocalyx length and stiffness, as revealed by atomic force microscopy. This TRF2-dependent regulation facilitated the recruitment of MDSCs, their …
Constitutive activation of JAK2 in mammary epithelium elevates Stat5 signalling, promotes alveologenesis and resistance to cell death, and contribute…
2011
Signalling through the janus kinase (JAK)/signal transducer and activator of transcription (Stat) pathway is required at different stages of mammary gland development, and this pathway is frequently hyper-activated in cancer, including tumours of the breast. Stats 3, 5 and 6 have important roles in the differentiation and survival of mammary alveolar cells, but somewhat paradoxically, both Stat3 and 5 can have oncogenic activity in the mammary gland. Constitutive activation of JAK2 could be anticipated to result in hyper-activation of Stats 1, 3, 5 and 6 with concomitant cell transformation, although the outcome is difficult to envisage, particularly since Stats 3 and 5 play opposing roles …
IL-6 receptor independent stimulation of human gp130 by viral IL-6.
2000
Abstract The genome of human herpes virus 8, which is associated with Kaposi’s sarcoma, encodes proteins with similarities to cytokines and chemokines including a homologue of IL-6. Although the function of these viral proteins is unclear, they might have the potential to modulate the immune system. For viral IL-6 (vIL-6), it has been demonstrated that it stimulates IL-6-dependent cells, indicating that the IL-6R system is used. IL-6 binds to IL-6R, and the IL-6/IL-6R complex associates with gp130 which dimerizes and initiates intracellular signaling. Cells that only express gp130 but no IL-6R cannot be stimulated by IL-6 unless a soluble form of the IL-6R is present. This type of signaling…
In vivo GSH depletion induces c-myc expression by modulation of chromatin protein complexes.
2009
Abstract We hypothesize that glutathione (GSH) fluctuations could have a prominent role in the modulation of c-myc expression through a mechanism affecting chromatin remodeling complexes. This could lead to an open chromatin structure accessible to transcription factors. We studied the in vivo effect of GSH depletion on these complexes bound to the c-myc promoter in the liver of l-buthionine-(S,R)-sulfoximine (BSO)-treated rats. Using chromatin immunoprecipitation we found that 3 h after BSO treatment the repressing complexes Id2 and Sin3A (part of a histone–deacetylase complex) were released from the c-myc promoter. STAT3 was phosphorylated and associated with its coactivator p300 with int…
Anti-inflammatory and joint protective effects of extra-virgin olive-oil polyphenol extract in experimental arthritis
2014
The consumption of extra virgin olive oil (EVOO) in Mediterranean countries has shown beneficial effects. A wide range of evidence indicates that phenolic compounds present in EVOO are endowed with anti-inflammatory properties. In this work, we evaluated the effects of EVOO-polyphenol extract (PE) in a model of rheumatoid arthritis, the collagen-induced arthritis model in mice. On day 0, DBA-1/J mice were immunized with bovine type II collagen. On day 21, mice received a booster injection. PE (100 and 200 mg/kg) was orally administered once a day from days 29 to 41 to arthritic mice. We have demonstrated that PE decreases joint edema, cell migration, cartilage degradation and bone erosion. …
The interleukin (IL)-31/IL-31R axis contributes to tumor growth in human follicular lymphoma
2014
Interleukin (IL)-31A binds to an heterodimer composed of IL-31 receptor A (IL-31RA) and Oncostatin M Receptor (OSMR). The IL-31/IL-31R complex is involved in the pathogenesis of various skin diseases, including cutaneous T-cell lymphoma. No information is available on the relations between the IL-31/IL-31R complex and B-cell lymphoma. Here we have addressed this issue in follicular lymphoma (FL), a prototypic germinal center(GC)-derived B-cell malignancy. IL-31 enhanced primary FL cell proliferation through IL-31R-driven signal transducer and activator of transcription factor 1/3 (STAT1/3), extracellular signal-regulated kinase 1/2 (ERK1/2) and Akt phosphorylation. In contrast, GC B cells d…
Extracellular Nampt promotes macrophage survival via a nonenzymatic interleukin-6/STAT3 signaling mechanism.
2008
Macrophages play key roles in obesity-associated pathophysiology, including inflammation, atherosclerosis, and cancer, and processes that affect the survival-death balance of macrophages may have an important impact on obesity-related diseases. Adipocytes and other cells secrete a protein called extracellular nicotinamide phosphoribosyltransferase (eNampt; also known as pre-B cell colony enhancing factor or visfatin), and plasma levels of eNampt increase in obesity. Herein we tested the hypothesis that eNampt could promote cell survival in macrophages subjected to endoplasmic reticulum (ER) stress, a process associated with obesity and obesity-associated diseases. We show that eNampt potent…
Interruption of Macrophage-Derived IL-27(p28) Production by IL-10 during Sepsis Requires STAT3 but Not SOCS3
2014
Abstract Severe sepsis and septic shock are leading causes of morbidity and mortality worldwide. Infection-associated inflammation promotes the development and progression of adverse outcomes in sepsis. The effects of heterodimeric IL-27 (p28/EBI3) have been implicated in the natural course of sepsis, whereas the molecular mechanisms underlying the regulation of gene expression and release of IL-27 in sepsis are poorly understood. We studied the events regulating the p28 subunit of IL-27 in endotoxic shock and polymicrobial sepsis following cecal ligation and puncture. Neutralizing Abs to IL-27(p28) improved survival rates, restricted cytokine release, and reduced bacterial burden in C57BL/…
Interleukin (IL)-22 receptor 1 is over-expressed in primary Sjogren's syndrome and Sjögren-associated non-Hodgkin lymphomas and is regulated by IL-18.
2015
Summary The aim of this study was to elucidate more clearly the role of interleukin (IL)-18 in modulating the IL-22 pathway in primary Sjögren's syndrome (pSS) patients and in pSS-associated lymphomas. Minor salivary glands (MSGs) from patients with pSS and non-specific chronic sialoadenitis (nSCS), parotid glands biopsies from non-Hodgkin lymphomas (NHL) developed in pSS patients, were evaluated for IL-18, IL-22, IL-22 receptor 1 (IL-22R1), IL-22 binding protein (IL-22BP) and signal transducer and activator of transcription-3 (STAT-3) expression. MSGs IL-22R1-expressing cells were characterized by confocal microscopy and flow cytometry in pSS, nSCS and healthy controls. The effect of recom…