Search results for "Downregulation"
showing 10 items of 460 documents
The Neuronal Nitric Oxide Synthase Is Upregulated in Mouse Skin Repair and in Response to Epidermal Growth Factor in Human HaCaT Keratinocytes
2004
Expression of nNOS mRNA was found in normal human and mouse skin tissue. Upon wounding, we observed a rapid downregulation of nNOS mRNA and protein in wounds of mice; however, when repair continued, nNOS mRNA was strongly upregulated and nNOS protein expression peaked at late stages of healing. Immunohistochemistry revealed wound keratinocytes as the cellular source of nNOS. In line with the in vivo situation, we found a basal expression of nNOS in the human keratinocyte cell line HaCaT. A marked stimulation of nNOS expression in the cells was achieved with epidermal growth factor receptor (EGFR) ligands such as epidermal growth factor (EGF), heparin-binding EGF, transforming growth factor-…
Avarol inhibits TNF-a generation and NF-kB activation in human cells and in animal models
2007
Avarol is a marine sesquiterpenoid hydroquinone with interesting pharmacological properties including anti-inflammatory and antipsoriatic effects. In the present study we evaluated the pharmacological effect of avarol on some inflammatory parameters related to the pathogenesis of psoriasis. Avarol inhibited tumor necrosis factor-alpha (TNF-alpha) generation in stimulated human monocytes (IC(50) 1 microM) and TNF-alpha-induced activation of nuclear factor-kappaB (NF-kappaB)-DNA binding in keratinocytes. In the mouse air pouch model, administration of avarol produced a dose-dependent reduction of TNF-alpha generation (ED(50) 9.2 nmol/pouch) as well as of interleukin (IL)-1beta, prostaglandin …
Resistance of keratinocytes to TGFbeta-mediated growth restriction and apoptosis induction accelerates re-epithelialization in skin wounds.
2002
The pleiotropic growth factor TGFβ plays an important role in regulating responses to skin injury. TGFβ targets many different cell types and is involved in all aspects of wound healing entailing inflammation,re-epithelialization, matrix formation and remodeling. To elucidate the role of TGFβ signal transduction in keratinocytes during cutaneous wound healing, we have used transgenic mice expressing a dominant negative type II TGFβ receptor exclusively in keratinocytes. We could demonstrate that this loss of TGFβ signaling in keratinocytes led to an accelerated re-epithelialization of full thickness excisional wounds accompanied by an increased proliferation in keratinocytes at the wound ed…
Downregulation of KLF8 expression by shRNA induces inhibition of cell proliferation in CAL27 human oral cancer cells
2013
Objectives: KLF8 is a member of KLF transcription factors which play an important tolr in oncogenesis. It is barely expressed in normal human epithelial cells but highly overexpressed in several types of human cancer cell lines. In the present study, we investigate the role of KLF8 in oral cancer and the effects of KLF8 knockdown via lentivirus mediated siRNA infection in human adenosquamos carcinoma CAL 27 cells. Study Design: �e developed a vector-based siRNA expression system that can induce RNAi in CAL 27 oral canDesign: �e developed a vector-based siRNA expression system that can induce RNAi in CAL 27 oral canesign: �e developed a vector-based siRNA expression system that can induce RN…
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…
Severe metabolic alterations in liver cancer lead to ERK pathway activation and drug resistance
2020
Background: The extracellular signal-regulated kinase (ERK) pathway regulates cell growth, and is hyper-activated and associated with drug resistance in hepatocellular carcinoma (HCC). Metabolic pathways are profoundly dysregulated in HCC. Whether an altered metabolic state is linked to activated ERK pathway and drug response in HCC is unaddressed. Methods: We deprived HCC cells of glutamine to induce metabolic alterations and performed various assays, including metabolomics (with 13C-glucose isotope tracing), microarray analysis, and cell proliferation assays. Glutamine-deprived cells were also treated with kinase inhibitors (e.g. Sorafenib, Erlotinib, U0126 amongst other MEK inhibitors). …
Evolutionary and transcriptional analyses of a pentraxin-like component family involved in the LPS inflammatory response of Ciona robusta
2020
Pentraxins (PTXs) are a superfamily of conserved proteins which are components of the humoral arm of innate immunity. They are considered to be functional ancestors of antibodies and are classified into short and long types. In this study, we show that a pentraxin-like component (Ptx-like) with a C-terminal PTX domain, highly homologous to the short PTX of H. sapiens CRP, and a long N-terminal domain typical of long PTXs, is involved in the inflammatory response of Ciona robusta under LPS exposure in vivo. Analyses of protein domains as well as 3D modelling and phylogenetic tree supported the close relationship of Ptx-like with mammalian CRP, suggesting that C. robusta Ptx-like shares a com…
Resveratrol decreases the levels of miR-155 by upregulating miR-663, a microRNA targeting JunB and JunD.
2010
An inflammatory component is present in the microenvironment of most neoplastic tissues, including those not causally related to an obvious inflammatory process. Several microRNAs, and especially miR-155, play an essential role in both the innate and adaptative immune response. Resveratrol (trans-3,4#,5-trihydroxystilbene) is a natural antioxidant with anti-inflammatory properties that is currently at the stage of preclinical studies for human cancer prevention. Here, we establish that, in human THP-1 monocytic cells as well as in human blood monocytes, resveratrol upregulates miR- 663, a microRNA potentially targeting multiple genes implicated in the immune response. In THP-1 cells, miR-66…
Reduced expression of TLR4 is associated with the metastatic status of human colorectal cancer.
2007
Signaling mediating colorectal cancer (CRC) progression is incompletely understood. Previously, we identified lipopolysaccharide (LPS), an endotoxin of ubiquitously existing colonic bacteria, as a pivotal stimulus increasing the metastatic potential of human CRC. Since the ubiquitous colonic bacteria release large amounts of LPS this observation could be of enormous relevance for the progression of CRC. In this study we present data contributing to the elucidation of its mode of action. Since both receptors CD14 and TLR4 act as LPS mediators, we determined their expression in various CRC cell lines and in 115 non-metastatic, lymphogenous-metastatic and haematogenous-metastatic CRC specimens…
Phosphate Groups in the Lipid A Moiety Determine the Effects of LPS on Hepatic Stellate Cells: A Role for LPS-Dephosphorylating Activity in Liver Fib…
2020
Alkaline phosphatase (AP) activity is highly upregulated in plasma during liver diseases. Previously, we demonstrated that AP is able to detoxify lipopolysaccharide (LPS) by dephosphorylating its lipid A moiety. Because a role of gut-derived LPS in liver fibrogenesis has become evident, we now examined the relevance of phosphate groups in the lipid A moiety in this process. The effects of mono-phosphoryl and di-phosphoryl lipid A (MPLA and DPLA, respectively) were studied in vitro and LPS-dephosphorylating activity was studied in normal and fibrotic mouse and human livers. The effects of intestinal AP were studied in mice with CCL4-induced liver fibrosis. DPLA strongly stimulated fibrogenic…