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Transforming growth factor-beta stimulation of lung fibroblast prostaglandin E2 production.
Get PDFTransforming growth factor-beta (TGF beta) stimulated the production of total protein, collagen, and fibronectin by normal human lung fibroblasts. The stimulatory response was maximal at 100 pM TGF beta and reversed toward control at higher concentrations. Inhibition of fibroblast prostaglandin (PG) synthesis enhanced TGF beta-induced stimulation of total protein, collagen, and fibronectin production and reversed the negative slope of the dose-response curve at high concentrations of TGF beta. Determination of the steady-state levels of Types I and III procollagens and fibronectin mRNAs employing specific cDNA probes demonstrated that inhibition of fibroblast PG production increased the stimulatory effect of TGF beta on the levels of these transcripts. Exogenous PGE2 abrogated the stimulatory effects of TGF beta. These findings suggest that fibroblast stimulation by TGF beta may be down-regulated by endogenous PG synthesized in response to TGF beta. This notion was supported by the demonstration that TGF beta markedly stimulated fibroblast PGE2 production. These results indicate that TGF beta-induced stimulation of fibroblast PGE2 production may be an autoregulatory control mechanism to limit the effects of TGF beta on connective tissue protein synthesis
Epidermal growth factor coordinately regulates the expression of prostaglandin G/H synthase and cytosolic phospholipase A2 genes in embryonic mouse cells.
Get PDFConfluent, primary cultures of mouse embryo palate mesenchyme (MEPM) cells are refractory to activation of phospholipase A2 (PLA2) by the calcium ionophore A23187. However, treatment of these cultures with epidermal growth factor (EGF) permits the cells to activate PLA2 in response to A23187. We have developed this finding by exploring molecular mechanisms by which growth factors modulate mobilization and metabolism of arachidonic acid. We found chronic treatment (\u3e 6 h) of confluent MEPM cells with EGF (a) increases their ability to metabolize exogenous arachidonic acid to prostaglandin E2 (PGE2) and (b) stimulated constitutive expression of activities of PLA2 and cyclooxygenase (CyOx). Immunoprecipitation of [35S]proteins and Western blot analysis revealed EGF treatment stimulated synthesis and accumulation of PLA2c, CyOx-1, and CyOx-2. Northern hybridization analysis revealed EGF increased the steady-state levels of a transcript for the high molecular weight, cytosolic PLA2 (PLA2c), and both the 2.8- and 4.2-kb transcripts for CyOx-1 and CyOx-2, respectively. In vitro nuclear transcription assays showed a parallel increase in the transcription rate of the genes corresponding to CyOx-1 and PLA2c, but not CyOx-2, in response to EGF. Treatment with EGF had no effect on either synthesis of the low molecular weight, group II PLA2, accumulation of its transcript, or the transcription rate of its gene. Coordinate regulation of activities of PLA2 and CyOx in response to EGF did not parallel the mitogenic effects of EGF on confluent MEPM cells
Alternative splicing of human prostaglandin G/H synthase mRNA and evidence of differential regulation of the resulting transcripts by transforming growth factor beta 1, interleukin 1 beta, and tumor necrosis factor alpha.
Get PDFProstaglandin G/H synthase (PGG/HS) is the rate-limiting enzyme in the conversion of arachidonic acid to prostaglandins and thromboxanes. We screened a human lung fibroblast cDNA library with an ovine PGG/HS cDNA and isolated a 2.3-kilobase clone (HCO-T9). Sequence analysis of this clone showed that (a) it contained the entire translated region of PGG/HS and (b) it displayed an in-frame splicing of the last 111 base pairs encoded by exon 9, which resulted in the elimination of the N-glycosylation site at residue 409. Polymerase chain reaction amplification with specific oligonucleotides of reverse-transcribed mRNA from diverse human tissues and cultured cells yielded 400- and 300-base pair fragments that corresponded, respectively, to the intact and spliced transcripts. The expression of these two transcripts in cultured human lung fibroblasts was differentially regulated by serum, transforming growth factor beta 1, interleukin 1 beta, tumor necrosis factor alpha, and phorbol 12-myristate 13-acetate, as each of these conditions stimulated preferentially the expression of the unspliced transcripts. The elimination of one of the four N-glycosylation sites by the alternative splicing of exon 9 and the differential regulation of this process by relevant cytokines and growth factors may represent a mechanism for the regulation of PGG/HS enzymatic activity under physiological or pathological conditions
A multi-output cost function for port terminals : some guidelines for regulation
Get PDFCargo handling in ports is a multioutput activity, as freight can arrive in many forms such as containers, bulk, rolling stock, or noncontainerized general cargo. In this paper Tovar, Jara-D?, and Trujillo analyze the operation of port terminals through the estimation of a multioutput cost model that uses monthly data on three firms located at the Las Palmas port in Spain. This permits the calculation of product-specific marginal costs, economies of scale (general and by firm), and economies of scope, which are key tools to help the regulators in their task.Economic Theory&Research,Environmental Economics&Policies,Decentralization,Transport and Trade Logistics,Business Environment,Environmental Economics&Policies,Airports and Air Services,Economic Theory&Research,Transport and Trade Logistics,Transport Security
Production and cost functions and their application to the port sector : a literature survey
Get PDFSeaports provide multiple services to ships, cargo, and passengers. These services can be performed by a combination of public and private initiatives. Usually, the role of public sector institutions is to regulate and supervise private firms. In performing that task public sector institutions require in-depth knowledge of firms'cost structure. This paper offers a review of the literature about ports'cost structure and of its implications for regulation. The paper argues that the operation of port terminals should be analyzed by means of multiproduct theory. This approach allows the calculation of several cost indicators (economies of scale, scope, and so forth) which are key tools to help regulators.Environmental Economics&Policies,Business Environment,Information Technology,Economic Theory&Research,Labor Policies,Economic Theory&Research,Environmental Economics&Policies,Business Environment,Business in Development,Information Technology
Regulation of transforming growth factor-beta 1 gene expression by glucocorticoids in normal human T lymphocytes.
Get PDFGlucocorticoids (GC) modulate immune function in a number of ways, including suppression of T cell proliferation and other IL-2-mediated T cell functions. These inhibitory effects are similar to those induced by transforming growth factor-beta 1 (TGF-beta 1), a cytokine with potent T cell inhibiting activities. We examined the hypothesis that GC effects may be at least partially achieved through modulation of the expression of the TGF-beta 1 gene in activated T cells. Normal T cells were cultured with or without purified phytohemagglutinin (PHA-p) and 4 beta-phorbol 12-myristate 13-acetate (PMA) in the presence or absence of the synthetic GC, dexamethasone (100-200 micrograms/ml). The production of latent and active forms of TGF beta by these cells were analyzed by immunoblotting and bioassays. The steady-state levels of TGF-beta 1 mRNA were analyzed in total RNA from these cells by Northern hybridizations using a human TGF-beta 1 cDNA. The results showed that dexamethasone caused an increase in TGF beta production and a dose-dependent two to fourfold increase in TGF-beta 1 mRNA in activated as well as in unstimulated T cells, 1 h after exposure of the cultures to the steroid. The increase in TGF-beta 1 mRNA levels by dexamethasone was further potentiated two to threefold by cycloheximide, suggesting that the steroid effect may be due to inhibition of the synthesis of proteins that decrease TGF-beta 1 gene transcription or the stability of its transcripts. Finally, in vitro nuclear transcription studies indicated the dexamethasone effects on TGF-beta 1 gene expression to be largely transcriptional
Regulation of human lung fibroblast alpha 1(I) procollagen gene expression by tumor necrosis factor alpha, interleukin-1 beta, and prostaglandin E2.
Get PDFWe investigated the participation of prostaglandin (PG) E2 in the regulation of the alpha 1(I) procollagen gene expression by tumor necrosis factor alpha (TNF alpha), and interleukin-1 beta (IL-1 beta) in normal adult human lung fibroblasts. TNF alpha (100 units/ml) and IL-1 beta (100 units/ml) stimulated the production of PGE2 and caused a dose-dependent inhibition of up to 54 and 66%, respectively, of the production of type I procollagen. Preincubation of cultures with indomethacin partially reversed the inhibition of procollagen production induced by the cytokines. Cytokine-stimulated endogenous fibroblast PG accounted for 35 and 68% of the inhibition induced by TNF alpha and IL-1 beta, respectively. Steady-state mRNA levels for alpha 1(I) procollagen paralleled the changes in collagen production. The transcription rate of the alpha 1(I) procollagen gene was reduced by 58% by TNF alpha and by 43% by IL-1 beta. Cytokine-stimulated endogenous PG production accounted for half of these effects. These results indicate that TNF alpha and IL-1 beta inhibit the expression of the alpha 1(I) procollagen gene in human lung fibroblasts at the transcriptional level by a PGE2-independent effect as well as through the effect of endogenous fibroblast PGE2 released under the stimulus of the cytokines
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The effects of acute posttraining injections of cocaine on spatial memory in C57BL/6 mice
Get PDFThe purpose of this study was to investigate the effects of cocaine on spatial memory consolidation using the Morris water maze. Specifically, male and female C57BL/6 mice were trained on a spatial water task, and then administered a single posttraining injection of saline or cocaine (1.25, 2.5, 5.0, or 20.0 mg/kg)
Metallicity dependence of turbulent pressure and macroturbulence in stellar envelopes
Full text linkMacroturbulence, introduced as a fudge to reproduce the width and shape of
stellar absorption lines, reflects gas motions in stellar atmospheres. While in
cool stars, it is thought to be caused by convection zones immediately beneath
the stellar surface, the origin of macroturbulence in hot stars is still under
discussion. Recent works established a correlation between the
turbulent-to-total pressure ratio inside the envelope of stellar models and the
macroturbulent velocities observed in corresponding Galactic stars. To probe
this connection further, we evaluated the turbulent pressure that arises in the
envelope convective zones of stellar models in the mass range 1-125 Msun based
on the mixing-length theory and computed for metallicities of the Large and
Small Magellanic Cloud. We find that the turbulent pressure contributions in
models with these metallicities located in the hot high-luminosity part of the
Hertzsprung-Russel (HR) diagram is lower than in similar models with solar
metallicity, whereas the turbulent pressure in low-metallicity models
populating the cool part of the HR-diagram is not reduced. Based on our models,
we find that the currently available observations of hot massive stars in the
Magellanic Clouds appear to support a connection between macroturbulence and
the turbulent pressure in stellar envelopes. Multidimensional simulations of
sub-surface convection zones and a larger number of high-quality observations
are necessary to test this idea more rigorously.Comment: Accepted A&A, 8 p
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