Search results for "Downregulation"
showing 10 items of 460 documents
Expressional downregulation of neuronal-type NO synthase I in guinea pig skeletal muscle in response to bacterial lipopolysaccharide
1997
AbstractWe have investigated the expression of neuronal-type NO synthase I (NOS I) and inducible-type NOS II in guinea pig skeletal muscle (diaphragm). Expression of NOS I mRNA and protein was highest in muscle of specific pathogen-free animals, lower in normally bred animals, and lowest in lipopolysaccharide (LPS)-treated animals. NOS II mRNA and protein levels were highest in muscle of LPS-treated animals. Elevated NOS activity in muscle from LPS-treated animals was less susceptible to the NOS I-selective inhibitor NG-nitro-l-arginine. Expressional downregulation of NOS I in sepsis may have implications for contractile function of skeletal muscle.
Transcriptional up-regulation of nNOS in the dorsal vagal complex during low endotoxemia
2005
The present study analyses the expression and distribution of neuronal nitric oxide synthase (nNOS) in the brainstem of animals pre-treated with Escherichia coli or Helicobacter pylori LPS, at doses that modulate gastric motor function. Systemic administration of H. pylori LPS prevented in a dose-dependent manner (5, 40 and 100 microg kg(-1), i.v.) the increase in intragastric pressure induced by 2-deoxy-D-glucose (200 mg kg(-1), i.v.) in urethane-anaesthetized rats. Quantitative analysis showed a significant increase in the amount of nNOS mRNA induced by E. coli or H. pylori LPS (2 h later), in a segment of the brainstem containing the dorsal vagal complex (DVC). Immunohistochemical studie…
The RNA binding protein tristetraprolin influences the activation state of murine dendritic cells
2010
Abstract Dendritic cells (DCs) serve to maintain peripheral tolerance under steady state conditions. Upon triggering by activation signals they initiate strong immune responses. The activation of DCs is accompanied by a rapid upregulation of proinflammatory cytokines, which were shown in other cell types to be regulated by mechanisms at the transcriptional and posttranscriptional level. Tristetraprolin (TTP), an important RNA binding protein, is involved in the regulation of mRNA stability of such cytokines. In this study we analyzed the significance of TTP for mouse DCs, which were derived from TTP −/− and WT bone marrow progenitor cells (BM-DCs). Unstimulated BM-DCs of TTP −/− mice expres…
Ciona intestinalis galectin (CiLgals-a and CiLgals-b) genes are differentially expressed in endostyle zones and challenged by LPS
2015
Abstract Immunohistochemical and in situ hybridization assays were performed to answer the question whether the endostyle, that is the initial gastro-intestinal trait of Ciona intestinalis pharynx, is involved in galectin (CiLgals-a and CiLgals-b) production during the pharynx inflammatory response to LPS inoculation. Specific anti-CiLgal-a and anti-CiLgals-b antibodies, and oligonucleotide probes, that mark inflammatory hemocytes inside the pharynx vessels and vessel epithelium as shown by a previous paper, were assayed on endostyle histological sections. For the first time, we show that galectins are produced by endostyle zones, and both CiLgals-a and –b genes are upregulated by LPS. CiLg…
Quaking and miR-155 interactions in inflammation and leukemogenesis.
2015
Quaking (QKI) is a tumor-suppressor gene encoding a conserved RNA-binding protein, whose expression is downregulated in several solid tumors. Here we report that QKI plays an important role in the immune response and suppression of leukemogenesis. We show that the expression of Qki is reduced in lipopolysaccharide (LPS)-challenged macrophages, suggesting that Qki is a key regulator of LPS signaling pathway. Furthermore, LPS-induced downregulation of Qki expression is miR-155-dependent. Qki overexpression impairs LPS-induced phosphorylation of JNK and particularly p38 MAPKs, in addition to increasing the production of anti-inflammatory cytokine IL-10. In contrast, Qki ablation decreases Fas …
Deletion of organic cation transporter Oct3 promotes hepatic fibrosis via upregulation of TGFβ
2019
Organic cation transporters (OCT) are responsible for the intracellular uptake and detoxification of a broad spectrum of endogenous and exogenous substrates. OCTs are downregulated in cholestasis, fibrosis, and hepatocellular carcinoma, but the underlying molecular mechanisms and downstream effects of OCT deletion are unknown. Oct3-knockout ( Oct3−/−; FVB.Slc22a3tm10pb) and wild-type (WT; FVB) mice were subject to escalating doses of carbon tetrachloride (CCl4) or thioacetamide (TAA) for 6 wk to induce advanced parenchymal liver fibrosis. Secondary biliary fibrosis was generated by bile duct ligation. Liver fibrosis was assessed by hydroxyproline determination, quantitative Sirius red morp…
Interleukin-10 expression is autoregulated at the transcriptional level in human and murine kupffer cells
1998
Interleukin 10 (IL-10) is known to downregulate immune responses. The regulation of IL-10 gene expression therefore determines the outcome of local immune reactions. We investigated time course and downregulation of IL-10 production in primary Kupffer's cells (KC), which are known to secrete IL-10 in response to endotoxin challenge. Human and murine KC were isolated by centrifugal elutriation and investigated for IL-10 gene expression by a two-step amplification procedure (reverse transcriptase-polymerase chain reaction [PCR] followed by T7-polymerase chain reaction). We show that IL-10 messenger ribonucleic acid (mRNA) showed a >450 fold increase in KC 2 hours after endotoxin challenge. IL…
Macrophages govern antiviral responses in human lung tissues protected from SARS-CoV-2 infection
2021
SUMMARYThe majority of SARS-CoV-2 infections among healthy individuals result in asymptomatic to mild disease. However, the immunological mechanisms defining effective lung tissue protection from SARS-CoV-2 infection remain elusive. Unlike mice solely engrafted with human fetal lung xenograft (fLX), mice co-engrafted with fLX and a myeloid-enhanced human immune system (HNFL mice) are protected against SARS-CoV-2 infection, severe inflammation, and histopathology. Effective control of viral infection in HNFL mice associated with significant macrophage infiltration, and the induction of a potent macrophage-mediated interferon response. The pronounced upregulation of the USP18-ISG15 axis (a ne…
HSPH1 inhibition downregulates Bcl-6 and c-Myc and hampers the growth of human aggressive B-cell non-Hodgkin lymphoma
2015
We have shown that human B-cell non-Hodgkin lymphomas (B-NHLs) express heat shock protein (HSP)H1/105 in function of their aggressiveness. Here, we now clarify its role as a functional B-NHL target by testing the hypothesis that it promotes the stabilization of key lymphoma oncoproteins. HSPH1 silencing in 4 models of aggressive B-NHLs was paralleled by Bcl-6 and c-Myc downregulation. In vitro and in vivo analysis of HSPH1-silenced Namalwa cells showed that this effect was associated with a significant growth delay and the loss of tumorigenicity when 10(4) cells were injected into mice. Interestingly, we found that HSPH1 physically interacts with c-Myc and Bcl-6 in both Namalwa cells and pr…
BRAFV600E mutation, TIMP-1 upregulation, and NF-κB activation: closing the loop on the papillary thyroid cancer trilogy.
2011
BRAFV600E is the most common mutation found in papillary thyroid carcinoma (PTC). Tissue inhibitor of metalloproteinases (TIMP-1) and nuclear factor (NF)-κB have been shown to play an important role in thyroid cancer. In particular, TIMP-1 binds its receptor CD63 on cell surface membrane and activates Akt signaling pathway, which is eventually responsible for its anti-apoptotic activity. The aim of our study was to evaluate whether interplay among these three factors exists and exerts a functional role in PTCs. To this purpose, 56 PTC specimens were analyzed for BRAFV600E mutation, TIMP-1 expression, and NF-κB activation. We found that BRAFV600E mutation occurs selectively in PTC nodules an…