scholarly journals Glucocorticoids potentiate IL-6-induced SP-B expression in H441 cells by enhancing the JAK-STAT signaling pathway

2010 ◽  
Vol 299 (4) ◽  
pp. L578-L584 ◽  
Author(s):  
Andreas Ladenburger ◽  
Matthias Seehase ◽  
Boris W. Kramer ◽  
Wolfgang Thomas ◽  
Johannes Wirbelauer ◽  
...  
Keyword(s):  
Gene Expression ◽  
Signaling Pathway ◽  
Synergistic Effects ◽  
Regulation System ◽  
Mrna Levels ◽  
Α Subunit ◽  
Steroid Administration ◽  
Stat3 Phosphorylation ◽  
Antenatal Steroid ◽  
Stat Signaling

The respiratory distress syndrome (RDS) contributes to perinatal morbidity and mortality associated with preterm birth. Surfactant protein B (SP-B) is decreased in RDS. Both maternal antenatal steroid administration and chorioamnionitis reduce the incidence and severity of RDS. An important mediator in chorioamnionitis is IL-6 using the JAK-STAT signaling pathway for signal transduction. We hypothesized that the steroids, betamethasone (BTM) and dexamethasone (DXM), and IL-6 had synergistic effects on SP-B gene expression and STAT3 phosphorylation in H441 cells. DXM and BTM increased SP-B mRNA levels by 16.5 (13.3)-fold and IL-6 alone by 2.3-fold. After 48-h exposure of cells to DXM or BTM, IL-6 caused a significantly greater increase in SP-B mRNA levels (28.1-fold) than IL-6 or glucocorticoids alone. Whereas IL-6 stimulated tyrosine phosphorylation of STAT3 in a time- and dose-dependent way, DXM and BTM had no effect on STAT3 phosphorylation. Both DXM and BTM could potentiate IL-6-induced phosphorylation of STAT3. The synergism of glucocorticoids and IL-6 on SP-B gene expression and the effect of glucocorticoids on IL-6-induced STAT3 phosphorylation could be blocked by a JAK inhibitor. Expression level analysis showed that glucocorticoids increased the expression of the IL-6-binding α-subunit receptor (IL-6R) on mRNA and protein level. Our findings could represent an example of a pulmonary regulation system in which one role of glucocorticoids is to increase the effect of a cytokine by upregulation of its receptor. The described in vitro interaction of IL-6 and glucocorticoids could help explain the clinical observation that prenatal inflammation in preterm babies with antenatal steroid administration can attenuate severity of RDS.

scholarly journals Kyungheechunggan-Tang-01, a New Herbal Medication, Suppresses LPS-Induced Inflammatory Responses through JAK/STAT Signaling Pathway in RAW 264.7 Macrophages

2017 ◽  
Vol 2017 ◽  
pp. 1-15 ◽  
Author(s):  
Hee-Soo Han ◽  
Eungyeong Jang ◽  
Ji-Sun Shin ◽  
Kyung-Soo Inn ◽  
Jang-Hoon Lee ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Inflammatory Responses ◽  
Inflammatory Diseases ◽  
Molecular Data ◽  
Mrna Levels ◽  
Protein Levels ◽  
Stat3 Phosphorylation ◽  
Stat Signaling ◽  
Cox 2 ◽  
Anti Inflammatory

Medicinal plants have been used as alternative therapeutic tools to alleviate inflammatory diseases. The objective of this study was to evaluate anti-inflammatory properties of Kyungheechunggan-tang- (KCT-) 01, KCT-02, and Injinchunggan-tang (IJCGT) as newly developed decoctions containing 3–11 herbs in LPS-induced macrophages. KCT-01 showed the most potent inhibitory effects on LPS-induced NO, PGE2, TNF-α, and IL-6 production among those three herbal formulas. In addition, KCT-01 significantly inhibited LPS-induced iNOS and COX-2 at protein levels and expression of iNOS, COX-2, TNF-α, and IL-6 at mRNA levels. Molecular data revealed that KCT-01 attenuated the activation of JAK/STAT signaling cascade without affecting NF-κB or AP-1 activation. In ear inflammation induced by croton oil, KCT-01 significantly reduced edema, MPO activity, expression levels of iNOS and COX-2, and STAT3 phosphorylation in ear tissues. Taken together, our findings suggest that KCT-01 can downregulate the expression of proinflammatory genes by inhibiting JAK/STAT signaling pathway under inflammatory conditions. This study provides useful data for further exploration and application of KCT-01 as a potential anti-inflammatory medicine.

Abstract 12559: Rapid Atrial Pacing Augments Fibrinogen Expression With Activation of IL-6/STAT3 Signaling Pathway in the Rat Liver

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Takanori Yaegashi ◽  
Takeshi Kato ◽  
Soichiro Usui ◽  
Naomi Kanamori ◽  
Hiroshi Furusho ◽  
...  
Keyword(s):  
Gene Expression ◽  
Signaling Pathway ◽  
Peripheral Blood ◽  
Blood Cells ◽  
Atrial Pacing ◽  
Peripheral Blood Cells ◽  
Stat3 Signaling ◽  
Stat3 Signaling Pathway ◽  
Stat3 Phosphorylation ◽  
Atrial Excitation

Introduction: Atrial fibrillation (AF) activates coagulation system leading to hypercoagulation of the blood. However, it is still unknown whether rapid atrial excitation per se affects gene expression remotely in the liver, the major source of coagulation factors and other prothrombotic molecules. Methods and Results: The AF model was created by rapid atrial pacing at the frequency of 1200 bpm in anesthetized 10-week-old Sprague-Dawley rats. The livers and peripheral blood cells were collected and analyzed after the pacing of 12 hours. Sham-operated rats underwent the identical procedure without electrical stimulation. DNA microarray revealed marked changes in hepatic gene expression after 12 hours atrial pacing. Hierarchical clustering with 13871 filtered genes or genes related to coagulation including fibrinogen, demonstrated clusters for the pacing or sham. The quantitative RT-PCR focused on prothrombotic molecules revealed that rapid atrial pacing significantly augmented the hepatic mRNA expressions of fibrinogen α, β, γ-chain, prothrombin, antithrombin-III, plasminogen, and coagulation factor X. The increase of fibrinogen protein in the liver was also confirmed by Western blotting (Figure A). We further investigated the mechanism of enhanced fibrinogen production and identified increased IL-6 mRNA expression in the peripheral blood cells by rapid atrial pacing (Figure B). IL-6 was also prominent in CD11b positive cells infiltrated in the liver, and possibly promoted STAT3 phosphorylation in the nuclei of hepatocytes (Figure C). Conclusions: The rapid atrial excitation mimicking paroxysmal AF altered the hepatic gene expressions of prothrombotic molecules. Increased fibrinogen expression in the liver was accompanied by activation of IL-6/STAT3 signaling pathway in the peripheral blood and the liver. These findings might imply the cardio-hepatic interaction in AF and provide new insight into the prevention of AF-related thromboembolism.

Gene expression after resumption of development of Artemia franciscana cryptobiotic embryos

1994 ◽  
Vol 72 (3-4) ◽  
pp. 78-83 ◽  
Author(s):  
Ricardo Escalante ◽  
Alberto García-Sáez ◽  
Maria-Asunción Ortega ◽  
Leandro Sastre
Keyword(s):  
Gene Expression ◽  
Time Course ◽  
Developmental Stages ◽  
Artemia Franciscana ◽  
Mrna Levels ◽  
Muscle Actin ◽  
Mrna Accumulation ◽  
Α Subunit ◽  
Steady State Levels ◽  
Cyst Development

The steady-state levels of six different mRNAs have been studied during Artemia franciscana development. Some of these mRNAs are present in the cryptobiotic cyst, like those coding for cytoplasmic actins, sarcoplasmic/endoplasmic reticulum Ca2+-ATPase, and the Na+,K+-ATPase α-subunit isoform coded by the clone pArATNa136. The expression of these mRNAs is markedly induced during cyst development. A small increase in mRNA levels can be observed for some genes at very early stages of development (2 h). The main increase is observed between 4 and 16 h of development for all these genes, although the time course of mRNA accumulation is different for each one of the genes studied. Some other genes, like those coding for muscle actin (actin 3) or the Na+,K+-ATPase α-subunit isoform coded by the cDNA clone α2850, are not expressed in the cyst before resumption of development and their expression is induced after 10 or 6 h of development, respectively. These data on the kinetic of mRNA accumulation provide the information required to determine transcriptionally active developmental stages, necessary to study in more detail the mechanisms of transcriptional regulation during activation of cryptobiotic cysts and resumption of embryonic development.Key words: Artemia, gene expression, actin, Na,K-ATPase, Ca2+-ATPase.

scholarly journals Regulation of pituitary inhibin/activin subunits and follistatin gene expression by GnRH in female rats

2011 ◽  
Vol 210 (1) ◽  
pp. 71-79 ◽  
Author(s):  
Petra Popovics ◽  
Zoltan Rekasi ◽  
Alan J Stewart ◽  
Magdolna Kovacs
Keyword(s):  
Gene Expression ◽  
Mrna Level ◽  
Inhibin B ◽  
Female Rats ◽  
Pituitary Cells ◽  
Mrna Levels ◽  
Short Term ◽  
Α Subunit ◽  
Long Term Treatment

Pituitary inhibin B, activin B, and follistatin are local regulators of FSH. Activin B is a homodimeric molecule (βB–βB), while inhibin B contains an α and a βB subunit. The regulation of gene expression of α, βB, and follistatin by local and endocrine hormones was examined in pituitaries from female rats and in perifused pituitary cells by RT-PCR. Ovariectomy (OVX) induced an elevation in the mRNA level of α and βB subunits and follistatin. Short-term (4 h) treatment of pituitary cells with GnRH decreased both the inhibin α and the inhibin/activin βB subunit mRNA levels, while long-term treatment (20 h) with 100 nM GnRH stimulated the expression of both subunits. In contrast, the mRNA level of follistatin was elevated after the short-term GnRH treatment. Long-term exposure of pituitary cells to estradiol and inhibin B suppressed the mRNA expression of βB and had no effect on the expression of α subunit and follistatin. Our results demonstrate that the increased expressions of inhibin/activin subunits and follistatin in the post-OVX period can be induced by the lack of gonadal negative feedback, resulting in a high GnRH environment in the pituitary. This study reports for the first time that GnRH administered in high doses and for a long period stimulates the gene expression of inhibin/activin subunits and thereby may contribute to the stimulatory effect of OVX on the expression of these genes.

Abstract 570: A Functional Mutation in WNT16a Up-regulates Pancreatic Expression of TCF7L2 Variants Through Wnt Signaling Pathway

2013 ◽  
Vol 33 (suppl_1) ◽  
Author(s):  
Asma Saleem ◽  
Eric W Howard ◽  
Latonya F Been ◽  
Megan Lerner ◽  
Daniel Brackett ◽  
...  
Keyword(s):  
Wnt Signaling ◽  
Signaling Pathway ◽  
Cell Function ◽  
Synergistic Effects ◽  
Wnt Signaling Pathway ◽  
Upstream Open Reading Frame ◽  
Dependent Diabetes Mellitus ◽  
Translation Initiation Site ◽  
Mrna Levels

Type 2 (non-insulin-dependent) diabetes mellitus (T2DM) is associated with a marked increase in the risk of coronary heart disease. The discovery of TCF7L2 as a global T2DM gene has triggered investigations to explore the clinical utility of its variants for guiding the development of new diagnostic and therapeutic strategies. However, interpreting the resulting associations into function still remains unclear. Canonical Wnt signaling regulates β-catenin and its binding with TCF7L2, which in turn is critical for the production of glucagon like protein-1 (GLP-1). This study examines the role of a novel frame-shift insertion discovered in a conserved region of WNT16a, and it is proposed that this mutation affects T2DM susceptibility in conjunction with gene variants in TCF7L2. Our results predicted that the insertion would convert the upstream open reading frame in the Wnt16a mRNA to an alternative, in-frame translation initiation site, resulting in the prevention of nonsense-mediated decay that would normally occur in the wild-type message, leading to a consequent stabilization of the mutated WNT16a message. To examine the role of Wnt16a in the Wnt signaling pathway, DNA and serum samples from 2,034 individuals (48% with T2DM) from the Sikh Diabetes Study were used in this investigation, of which 32% were WNT16a insertion carriers. There was a 3.2 fold increase in Wnt16a mRNA levels in pancreatic tissues from the insertion carriers and a significant increase (70%, p<0.0001) in luciferase activity in the constructs carrying the insertion. The expression of TCF7L2 mRNA in pancreas was also elevated (~23-fold) among the insertion carriers (p=0.003). Our results suggest synergistic effects of WNT16a insertion mutants and the at-risk ‘T ‘allele of TCF7L2 (rs7903146) for compounding the risk of T2DM, perhaps by impacting genes related to β-cell function in the Wnt/β-catenin/TCF7L2 signaling pathway.

scholarly journals CXCL12 Regulates the Cholinergic Locus and CHT1 Through Akt Signaling Pathway

2016 ◽  
Vol 40 (5) ◽  
pp. 982-992 ◽  
Author(s):  
Jing Yan ◽  
Wenhui Zhao ◽  
Meixia Guo ◽  
Xuefei Han ◽  
Zhiwei Feng
Keyword(s):  
Gene Expression ◽  
Signaling Pathway ◽  
Choline Acetyltransferase ◽  
Cholinergic Neurons ◽  
Akt Signaling ◽  
Neuronal Cultures ◽  
Mrna Levels ◽  
Akt Signaling Pathway ◽  
The Impact ◽  
And Storage

Background: CXCL12 is pivotal for cholinergic neurons, and it induces the expressions of several genes that are essential for synthesis and storage of acetylcholine(ACh), specifically choline acetyltransferase, vesicular ACh transporter (VAChT), and choline transporter. The present study explored the impact of pharmacological Akt inhibition upon cholinergic gene expression. Methods: Western blotting was employed to determine the level of p-AKT, RT-PCR to check the mRNA levels of and CHT1(choline transporter1),VAChT and ChAT, ELISA to decipher the secretion of ACh and the activity of choline acetyltransferase. Results: Here we demonstrated, in the rat pheochromocytoma cell line PC12 and in primary rat neuronal cultures, that CXCL12-evoked up-regulation of CHT1, VAChT and ChAT was mediated by Akt. Inhibition of Akt by the pharmacological inhibitor GSK690693 eliminated CXCL12-stimulated increases in cholinergic gene expression. Moreover, treatment with GSK690693 reversed CXCL12-evoked increases in choline acetyltransferase activity and ACh production. Conclusion: Our results suggest that CXCL12 contributes to cholinergic gene expression via Akt signaling pathway.

Seawater tolerance and gene expression in two strains of Atlantic salmon smolts

2002 ◽  
Vol 59 (1) ◽  
pp. 125-135 ◽  
Author(s):  
Thomas D Singer ◽  
Koreen M Clements ◽  
Jeffrey W Semple ◽  
Patricia M Schulte ◽  
Jason S Bystriansky ◽  
...  
Keyword(s):  
Gene Expression ◽  
Atlantic Salmon ◽  
Atpase Activity ◽  
Mrna Levels ◽  
Transmembrane Conductance Regulator ◽  
Transmembrane Conductance ◽  
Α Subunit ◽  
Seawater Tolerance ◽  
Mrna And Protein Expression ◽  
Or Gene

The seawater tolerance of Atlantic salmon (Salmo salar) smolts reared under identical hatchery conditions was assessed in two Norwegian strains: AquaGen and Imsa. Plasma ion levels were disrupted in both strains following seawater exposure, but these disruptions were more profound in the AquaGen fish. To investigate the mechanisms underlying these differences, we measured gill Na+,K+-adenosine triphosphatase (ATPase) activity and mRNA levels of Na+,K+-ATPase α-subunit and two isoforms of the cystic fibrosis transmembrane conductance regulator (CFTR). Gill Na+,K+-ATPase activity rose significantly in both strains following seawater exposure. Both Na+,K+-ATPase α-subunit and CFTR I mRNA levels were significantly elevated for the entire 2-week period following seawater exposure, whereas CFTR II levels were transiently elevated during the first 24 h only. There were no differences in enzyme activity or gene expression between strains, with the exception of CFTR II, which was significantly lower in the Imsa strain 2 weeks following seawater exposure. This suggests that although changes in mRNA and protein expression for these genes are associated with seawater transfer, they are not the basis of observed physiological differences between strains.

scholarly journals Activation of the STAT signaling pathway can cause expression of caspase 1 and apoptosis.

1997 ◽  
Vol 17 (9) ◽  
pp. 5328-5337 ◽  
Author(s):  
Y E Chin ◽  
M Kitagawa ◽  
K Kuida ◽  
R A Flavell ◽  
X Y Fu
Keyword(s):  
Gene Expression ◽  
Cell Line ◽  
Signaling Pathway ◽  
Hela Cells ◽  
Similar Response ◽  
Dependent Manner ◽  
Ifn Gamma ◽  
Caspase 1 ◽  
Stat Signaling ◽  
Induced Apoptosis

Protein tyrosine kinases activate the STAT (signal transducer and activator of transcription) signaling pathway, which can play essential roles in cell differentiation, cell cycle control, and development. However, the potential role of the STAT signaling pathway in the induction of apoptosis remains unexplored. Here we show that gamma interferon (IFN-gamma) activated STAT1 and induced apoptosis in both A431 and HeLa cells, whereas epidermal growth factor (EGF) activated STAT proteins and induced apoptosis in A431 but not in HeLa cells. EGF receptor autophosphorylation and mitogen-activated protein kinase activation in response to EGF were similar in both cell lines. The breast cancer cell line MDA-MB-468 exhibited a similar response to A431 cells, i.e., STAT activation and apoptosis correlatively resulted from EGF or IFN-gamma treatment. In addition, in a mutant A431 cell line in which STAT activation was abolished, no apoptosis was induced by either EGF or IFN-gamma. We further demonstrated that both EGF and IFN-gamma induced caspase 1 (interleukin-1beta converting enzyme [ICE]) gene expression in a STAT-dependent manner. IFN-gamma was unable to induce ICE gene expression and apoptosis in either JAK1-deficient HeLa cells (E2A4) or STAT1-deficient cells (U3A). However, ICE gene expression and apoptosis were induced by IFN-gamma in U3A cells into which STAT1 had been reintroduced. Moreover, both EGF-induced apoptosis and IFN-gamma-induced apoptosis were effectively blocked by Z-Val-Ala-Asp-fluoromethylketone (ZVAD) in all the cells tested, and studies from ICE-deficient cells indicated that ICE gene expression was necessary for IFN-gamma-induced apoptosis. We conclude that activation of the STAT signaling pathway can induce apoptosis through the induction of ICE gene expression.

Abstract 438: Global Gene Expression Analysis of Human Perivascular Adipocytes Reveals Reduced Expression of Insulin and Wnt Signaling Genes: Implications for Inflammatory Crosstalk

2012 ◽  
Vol 32 (suppl_1) ◽  
Author(s):  
Tapan K Chatterjee ◽  
David G Kuhel ◽  
David Y Hui ◽  
Neal L Weintraub
Keyword(s):  
Gene Expression ◽  
Adipose Tissue ◽  
Wnt Signaling ◽  
Signaling Pathway ◽  
Insulin Signaling ◽  
Human Subjects ◽  
Adipogenic Differentiation ◽  
Expression Patterns ◽  
Mrna Levels ◽  
Altered Expression

Inflammatory crosstalk between PV adipose tissue and the blood vessel wall has been proposed to contribute to the pathogenesis of atherosclerosis. We reported that PV adipocytes exhibit a pro-inflammatory phenotype, reduced state of differentiation, and altered expression of developmental genes as compared with subcutaneous (SQ) adipocytes derived from the same human subjects. To define global differences in gene expression patterns between PV and SQ adipocytes, genome-wide microarray studies were performed in three sets of in vitro differentiated SQ and PV adipocytes derived from unrelated human subjects. Insulin-regulated and Wnt signaling genes were markedly down-regulated in PV adipocytes. Validation of microarray data by qPCR demonstrated reductions in expression of C/EBPα, PPARγ, FABP4, adiponectin, lipoprotein lipase, hormone sensitive lipase and perilipin in PV compared to SQ adipocytes. We further observed that insulin-induced Akt ser-473 phosphorylation and glucose uptake were markedly reduced (∼ 3 fold and 4 fold, respectively) in differentiated PV adipocytes compared to SQ adipocytes. The mRNA levels of insulin and insulin-like growth factor receptors, however, were similar in adipocytes differentiated from these two depots. Regarding the Wnt pathway, PV adipocytes exhibited dramatically elevated expression of Wnt inhibitor DKK1 (2864%) and reduced expression of Wnt 5A (50%), FDZ4 (38%), and LRP5 (38%). Further evaluation revealed that these Wnt signaling pathway genes, like those of the insulin signaling pathway, correlated with the extent of adipogenic differentiation. We propose that dysregulation of Wnt 5A/FDZ4 and insulin signaling pathways contributes to impaired adipogenic differentiation and insulin resistance in PV adipocytes. This, in turn, may contribute to heightened inflammatory crosstalk between PV adipose tissue and the vascular wall in the setting of atherosclerosis.

Regulation of myogenin protein expression in denervated muscles from young and old rats

2000 ◽  
Vol 279 (1) ◽  
pp. R179-R188 ◽  
Author(s):  
Tatiana Y. Kostrominova ◽  
Peter C. D. Macpherson ◽  
Bruce M. Carlson ◽  
Daniel Goldman
Keyword(s):  
Gene Expression ◽  
Transcription Factor ◽  
Protein Expression ◽  
Rna Expression ◽  
Mrna Levels ◽  
Denervated Muscle ◽  
Α Subunit ◽  
Specific Transcription Factor ◽  
Old Rats ◽  
Denervated Muscles

Myogenin is a muscle-specific transcription factor participating in denervation-induced increases in nicotinic ACh receptor (nAChR) gene expression. Although myogenin RNA expression in denervated muscle is well documented, surprisingly little is known about myogenin protein expression. Therefore, we assayed myogenin protein and RNA in innervated and denervated muscles from young (4 mo) and old (24–32 mo) rats and compared this expression to that of the nAChR α-subunit RNA. These assays revealed increased myogenin protein expression within 1 day of denervation, preceding detectable increases in nAChR RNA. By 3 days of denervation, myogenin and nAChR α-subunit RNA were increased 500- and 130-fold, respectively, whereas myogenin protein increased 14-fold. Interestingly, old rats (32 mo) had 6-fold higher myogenin protein and ∼80-fold higher mRNA levels than young rats. However, after denervation, expression levels were similar for young and old animals. The increased myogenin expression during aging, which tends to localize to small fibers, likely reflects spontaneous denervation and/or regeneration. Our results show that increased myogenin protein in denervated muscles correlates with the upregulation of its mRNA.

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