Heterogeneous modulation of acute-phase-reactant mRNA levels by interleukin-1 beta and interleukin-6 in the human hepatoma cell line PLC/PRF/5.
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ABSTRACT:
SUBMITTER: Steel DM
PROVIDER: S-EPMC1151259 | biostudies-other | 1991 Jul
REPOSITORIES: biostudies-other
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Project description:OBJECTIVE:This study was undertaken to evaluate glucocorticoid dosages and serologic findings in patients with giant cell arteritis (GCA) flares. METHODS:Patients with GCA were randomly assigned to receive double-blind dosing with either subcutaneous tocilizumab (TCZ) 162 mg weekly plus 26-week prednisone taper (TCZ-QW + Pred-26), every-other-week TCZ plus 26-week prednisone taper (TCZ-Q2W + Pred-26), placebo plus 26-week prednisone taper (PBO + Pred-26), or placebo plus 52-week prednisone taper (PBO + Pred-52). Outcome measures were prednisone dosage, C-reactive protein (CRP) level, and erythrocyte sedimentation rate (ESR) at the time of flare. RESULTS:One hundred patients received TCZ-QW + Pred-26, 49 received TCZ-Q2W + Pred-26, 50 received PBO + Pred-26, and 51 received PBO + Pred-52. Of the 149 TCZ-treated patients, 36 (24%) experienced flare, 23 (64%) of whom were still receiving prednisone (median dosage 2.0 mg/day). Among 101 PBO + Pred-treated patients, 59 (58%) experienced flare, 45 (76%) of whom were receiving prednisone (median dosage 5.0 mg/day). Many flares occurred while patients were taking >10 mg/day prednisone: 9 (25%) in the TCZ groups and 13 (22%) in the placebo groups. Thirty-three flares (92%) in TCZ-treated groups and 20 (34%) in PBO + Pred-treated groups occurred with normal CRP levels. More than half of the PBO + Pred-treated patients had elevated CRP levels without flares. Benefits of the TCZ and prednisone combination over prednisone alone for remission induction were apparent by 8 weeks. CONCLUSION:Most GCA flares occurred while patients were still receiving prednisone. Acute-phase reactant levels were not reliable indicators of flare in patients treated with TCZ plus prednisone or with prednisone alone. The addition of TCZ to prednisone facilitates earlier GCA control.
| S-EPMC6772126 | biostudies-literature
Project description:Exposure of isolated perfused rat livers to hypo-osmotic (225 mosmol/l) perfusion media for 3 h led to a decrease of about 60% in mRNA levels for phosphoenolpyruvate carboxy-kinase (PEPCK) compared with normo-osmotic (305 mosmol/l) perfusions. Conversely, PEPCK mRNA levels increased about 3-fold during hyperosmotic (385 mosmol/l) perfusions. The anisotonicity effects were not explained by changes in the intracellular cyclic AMP (cAMP) concentration or by changes of the extracellular Na+ or Cl- activity. Similar effects of aniso-osmolarity on PEPCK mRNA levels were found in cultured rat hepatoma H4IIE.C3 cells, the experimental system used for further characterization of the effect. Whereas during the first hour of anisotonic exposure no effects on PEPCK mRNA levels were detectable, near-maximal aniso-osmolarity effects were observed within the next 2-3 h. PEPCK mRNA levels increased sigmoidally with the osmolarity of the medium, and the anisotonicity effects were most pronounced upon modulation of osmolarity between 250 and 350 mosmol/l. The aniso-osmolarity effects on PEPCK mRNA were not affected in presence of Gö 6850, protein kinase C inhibitor. cAMP increased the PEPCK mRNA levels about 2.3-fold in normo-osmotic media, whereas insulin lowered the PEPCK mRNA levels to about 8%. The effects of cAMP and insulin were also observed during hypo-osmotic and hyperosmotic exposure, respectively, but the anisotonicity effects were not abolished in presence of the hormones. The data suggest that hepatocellular hydration affects hepatic carbohydrate metabolism also over a longer term by modulating PEPCK mRNA levels. This is apparently unrelated to protein kinase C or alterations of cAMP levels. The data strengthen the view that cellular hydration is an important determinant for cell metabolic function by extending its regulatory role in carbohydrate metabolism to the level of mRNA.
| S-EPMC1137528 | biostudies-other
Project description:Cytokine production is essential for innate and adaptive immunity against microbial invaders and must be tightly controlled. Cytokine messenger RNA (mRNA) is in constant flux between the nucleus and the cytoplasm and in transcription, splicing, or decay; such processes must be tightly controlled. Here, we report a novel function of Y-box-binding protein 1 (YB-1) in modulating interleukin-6 (IL-6) mRNA levels in a cell type-specific manner. In lipopolysaccharide (LPS)-stimulated macrophages, YB-1 interacts with IL-6 mRNA and actively transports it to the extracellular space by YB-1-enriched vesicles, resulting in the proper maintenance of intracellular IL-6 mRNA levels. YB-1 secretion occurs in a cell type-specific manner. Whereas macrophages actively secret YB-1, dendritic cells maintain it predominantly in the cytoplasm even in response to LPS. Intracellular YB-1 has the distinct function of regulating IL-6 mRNA stability in dendritic cells. Moreover, because LPS differentially regulates the expression of histone deacetylase 6 (HDAC6) in macrophages and dendritic cells, this stimulus might control YB-1 acetylation differentially in both cell types. Taken together, these results suggest a unique feature of YB-1 in controlling intracellular IL-6 mRNA levels in a cell type-specific manner, thereby leading to functions that are dependent on the extracellular and intracellular distribution of YB-1.
| S-EPMC4232504 | biostudies-literature
Project description:Liver cancer is the sixth most common cancer globally and the third leading cause of cancer-related death. Alcohol dehydrogenase families (ADHs), which predominantly exist in the livers of humans and animals, serve as essential enzymes in the metabolism of short-chain alcohols and ω-oxidation of certain fatty acids, playing crucial roles in numerous physiological processes. A cluster of genes consisting of seven alcohol dehydrogenase-encoding genes (ADH1A, ADH1B, ADH1C, ADH4, ADH5, ADH6 and ADH7) is situated on chromosome 4q and encodes ADHs. Loss of Chromosome 4q is a frequent occurrence in liver cancer, leading to the loss of an entire cluster of seven genes. As a result, there is typically a decrease in the expression of ADHs (ADH1A, ADH1B, ADH1C, ADH4 and ADH6) in liver cancer. Amongst these, ADH4 is the most substantially downregulated gene, which affects both overall survival (OS) and disease-free survival (DFS) in liver cancer patients. Furthermore, a thorough investigation was previously conducted to identify possible biomarkers for predicting liver cancer recurrence. The results showed that in liver cancer, ADH4 was significantly downregulated and this downregulation indicated a higher likelihood of recurrence in liver cancer patients. As a consequence, further research was conducted on the role of ADH4 in liver cancer progression.
2023-08-19 | GSE241204 | GEO
Project description:Fibrinogen-like protein 1 (FGL1) is a hepatocyte derived protein that is upregulated in regenerating rodent livers following partial hepatectomy. It has been implicated as a mitogen for liver cell proliferation. In this study, we show that recombinant human IL-6 induces FGL1 expression in Hep G2 cells in a pattern similar to those of acute phase reactants. Following induction of acute inflammation in rats by subcutaneous injection of turpentine oil, serum FGL1 levels are also enhanced. Although, a recent report suggests that FGL1 associates almost exclusively with the fibrin matrix, we report here that approximately 20% of the total plasma FGL1 remains free. The enhancement of FGL1 levels in vitro by IL-6 and its induction after turpentine oil injection suggest that it is an acute phase reactant. Its presence in bound and free forms in the blood also implies biological roles that extend beyond the proposed autocrine effect it has on hepatocytes during regeneration.
| S-EPMC2288651 | biostudies-literature
Project description:BackgroundHepatocellular carcinoma (HCC) is one of the most common cancers worldwide that is particularly refractory to chemotherapy. Several studies have proposed combination chemotherapy regimen for HCC treatment. However, these therapies are not effective in regressing tumor and prolonging survival of patient's suffering from HCC. Therefore, the development of more effective therapeutic tools and new strategies for the treatment of HCC are urgently needed. Over the last decade much attention has been focused on "bystander effect" as a possible therapeutic strategy for the treatment of certain human tumors. Interest in this therapeutic approach originated from numerous reports describing the radiation induced bystander effect. However, the knowledge about chemotherapy induced bystander effect is still limited. Hence, chemotherapy induced bystander phenomenon in hepatoma cells was explored by utilizing Mitomycin C (MMC).ResultsMMC induced bystander killing was observed only in hepatoma cells and it did not occur in cervical cancer cells. MMC induced bystander killing was transferable via medium. It occurred in co-cultured cells indicating the involvement of secreted as well as membrane bound factors. FasL and TRAIL were detected in the conditioned medium from treated cells. In medium transfer experiment, pre-treatment with EDTA (a broad range protease inhibitor) diminished MMC induced bystander killing. Following drug exposure, expression of Fas and TRAIL receptors increased and treatment with neutralizing antibodies against FasL and TRAIL inhibited bystander killing.ConclusionOur results highlight the therapeutic importance of MMC in the treatment of HCC and implicate role of membrane bound and secreted forms of FasL and TRAIL in MMC induced bystander killing.
| S-EPMC2770032 | biostudies-literature
Project description:Apolipoprotein B mRNA-editing enzyme, catalytic polypeptide 1 (APOBEC1) is an intestine-specific RNA-binding protein. However, inflammation or exposure to DNA-damaging agents can induce ectopic APOBEC1 expression, which can result in hepatocellular hyperplasia in animal models. To identify its RNA targets, FLAG-tagged APOBEC1 was immunoprecipitated from transfected HuH7.5 hepatocellular carcinoma cells and analyzed using DNA microarrays. The interleukin-8 (IL8) mRNA was the most abundant co-precipitated RNA. Exogenous APOBEC1 expression increased IL8 production by extending the half-life of the IL8 mRNA. A cluster of AU-rich elements in the 3'-UTR of IL8 was essential to the APOBEC1-mediated increase in IL8 production. Notably, IL8 mRNA did not co-immunoprecipitate with APOBEC1 from lysates of other cell types at appreciable levels; therefore, other factors may enhance the association between APOBEC1 and IL8 mRNA in a cell type-specific manner. A yeast two-hybrid analysis and siRNA screen were used to identify proteins that enhance the interaction between APOBEC1 and IL8 mRNA. Heterogeneous nuclear ribonucleoprotein Q (hnRNPQ) was essential to the APOBEC1/IL8 mRNA association in HuH7.5 cells. Of the seven hnRNPQ isoforms, only hnRNPQ6 enabled APOBEC1 to bind to IL8 mRNA when overexpressed in HEK293 cells, which expressed the lowest level of endogenous hnRNPQ6 among the cell types examined. The results of a reporter assay using a luciferase gene fused to the IL8 3'-UTR were consistent with the hypothesis that hnRNPQ6 is required for APOBEC1-enhanced IL8 production. Collectively, these data indicate that hnRNPQ6 promotes the interaction of APOBEC1 with IL8 mRNA and the subsequent increase in IL8 production.
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Project description:Human skin fibroblasts were exposed to various concentrations (from 0.01 to 5.0 units/ml) of human recombinant interleukin-1 alpha and interleukin-1 beta (IL-1 alpha and IL-1 beta). Both IL-1 alpha and IL-1 beta were found to increase dermatan-sulphate-proteoglycan (DSPG) core-protein mRNA levels. Maximal increase (3.0-fold) was seen at 48 h after addition of 1 unit of IL-1 beta/ml. In spite of the elevated DSPG-core-protein mRNA only a slight increase (from 10 to 18%) could be seen in the production of DSPG to cell-culture medium. No changes in the molecular mass of DSPG could be detected.
| S-EPMC1149141 | biostudies-other
Project description:The aim of this study was to explore the effects of bamboo vinegar powder on growth performance, diarrhea situation and mRNA expression levels of cytokines i.e., interleukin-10 (IL-10), interleukin-22 (IL-22), and interleukin-25 (IL-25) in immune organs of weaned piglets, and to accumulate theoretical data for the application of bamboo vinegar powder in weaned piglet production. Forty-five crossbred (Duroc × Landrace × Yorkshire, all male) weaned piglets with similar body weight (6.74 ± 0.17 kg) at 31 days of age were randomly assigned to 5 treatments with 3 replicates per treatment and 3 piglets in each replicate. The five treatments were as follows: CON (a basal diet), ANT (the basal diet + 0.12% antibiotics), BV1 (the basal diet + 0.1% bamboo vinegar powder), BV5 (the basal diet + 0.5% bamboo vinegar powder), BV10 (the basal diet + 1.0% bamboo vinegar powder). This experiment lasted 35 days. The growth performance and diarrhea situation were recorded. The relative mRNA expression levels of IL-10, IL-22 and IL-25 in liver, spleen, duodenum and mesenteric lymph nodes were detected by real-time PCR. Feed: gain of BV5 was significantly lower than that of CON (P < 0.05). In comparison with CON, diarrhea rate and diarrhea index of BV1 and BV5 all tended to decrease (P < 0.1). Compared with CON, mRNA expression level of IL-10 in liver of ANT tended to be lower (P < 0.1) and these of BV1, BV5 and BV10 were significantly reduced (P < 0.05). The mRNA expression levels of IL-10 in duodenum of ANT, BV1, BV5 and BV10 were all lower than those of CON, of which BV10 had significantly decreased IL-10 mRNA expression in duodenum (P < 0.05). The mRNA expression levels of IL-22 in duodenum of ANT, BV1, BV5 and BV10 all tended to be inhibited compared with CON (P < 0.1). With the increase of bamboo vinegar powder dosage, mRNA expression levels of IL-25 in spleen and mesenteric lymph nodes of BV1, BV5 and BV10 tended to be up-regulated. Overall, bamboo vinegar powder could improve growth performance, and regulate mRNA expression levels of IL-10, IL-22 and IL-25 in immune organs of weaned piglets. The dosage at 0.5% showed optimum effects.
| S-EPMC5941013 | biostudies-literature
Project description:BackgroundProinflammatory cytokines play a critical role in antiviral immune responses. Large-scale genome studies have found correlations between single-nucleotide polymorphisms (SNPs) in the interleukin (IL) 18 promoter and spontaneous control of hepatitis C virus (HCV), suggesting a role in clearance.MethodsPlasma IL-18, IL-1β, IL-6, IL-8, IL-12, interferon-γ, tumor necrosis factor-α, alanine aminotransferase (ALT), and HCV RNA levels were assessed longitudinally in subjects with known dates of HCV acquisition and analyzed according to IL-18 SNPs and outcome, either spontaneous clearance (SC) (n = 13) or persistent infection (PI) (n = 25).ResultsNo significant change in plasma proinflammatory cytokine expression was observed with the exception of IL-18, which increased in every subject with initial detection of HCV RNA. In every SC subject, IL-18 returned to the preinfection baseline concomitant with HCV control. In PI subjects, IL-18 declined following the acute phase of infection but remained above the preinfection baseline throughout chronic infection and did not correlate with HCV RNA or ALT levels.ConclusionsPlasma IL-18 was an early and the most reliably detected host response to HCV infection measured in blood. Reduced IL-18 production with transition to chronic infection without correlation with HCV RNA or ALT levels suggests modulation of the innate response with persistent infection.
| S-EPMC3203233 | biostudies-literature