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At least 343 records · Page 19Linked to original sources
PubMed1993

Astrocyte expression of mRNA encoding cytokines IP-10 and JE/MCP-1 in experimental autoimmune encephalomyelitis.

Mononuclear leukocytes preferentially accumulate in the central nervous system (CNS) during the course of experimental autoimmune encephalomyelitis (EAE). To address factors that govern leukocyte trafficking in EAE, we monitored expression of mRNAs encoding IP-10 and JE/MCP-1, which are members of a family of chemoattractant cytokines. A transient burst of IP-10 and JE/MCP-1 mRNA accumulation in the CNS occurred, in close relation to the onset of histologic and clinical disease. In situ hybridizations showed, unexpectedly, that astrocytes were the major source of mRNAs encoding IP-10 and JE/MCP-1. These observations implicate astrocyte-derived cytokines as potential chemoattractants for inflammatory cells during EAE.

Animals↗
PubMed2006

Endothelial cell-T lymphocyte interactions: IP[corrected]-10 stimulates rapid transendothelial migration of human effector but not central memory CD4+ T cells. Requirements for shear stress and adhesion molecules.

The chemokine interferon (IFN)-gamma-inducible protein of 10 kDa (IP-10; CXCL10) has been implicated in recruitment of T cells into rejecting allografts yet appears ineffective at stimulating human peripheral blood CD4 T cells to transmigrate across tumor necrosis factor (TNF)-treated human endothelial cell (EC) monolayers in vitro. The same cells rapidly (within 15 min) transmigrate across TNF-treated EC monolayers overlaid with stromal cell-derived factor-1 alpha (SDF-1 alpha) and subjected to shear stress. The effector memory subset within the CD4 T cell population, defined as CD45RO, CD62L and CCR7, which constitutes less than 10% of total CD4 T cells, does respond to IP-10 but requires enrichment to be observed in this model. Central memory T cells do not respond to IP-10. Transendothelial migration of effector memory CD4 T cells requires TNF-pretreatment of the EC monolayer and application of venular shear force during the assay. TNF treatment of ECs may be effectively replaced by transduction of vascular cell adhesion molecule-1 or intercellular adhesion molecule-1 but not E-selectin.

CD4-Positive T-Lymphocytes↗
PubMed2006

Singularity characteristics of needle EMG IP signals.

Clinical electromyography (EMG) interference pattern (IP) signals can reveal more diagnostic information than their constituents, the motor unit action potentials (MUAPs). Singularities and irregular structures typically characterize the mathematically defined content of information in signals. In this paper, a wavelet transform method is used to detect and quantify the singularity characteristics of EMG IP signals using the Lipschitz exponent (LE) and measures derived from it. The performance of the method is assessed in terms of its ability to discriminate healthy, myopathic and neuropathic subjects and how it compares with traditionally used Turns Analysis (TA) methods and a method recently developed by the authors, interscale wavelet maximum (ISWM). Highly significant intergroup differences were found using the LE method. Most of the singularity measures have a performance similar to that of ISWM and considerably better than that of TA. Some measures such as the ratio of the mean LE value to the number of singular points in the signal have considerably superior performance to both methods. These findings add weight to the view that wavelet analysis methods offer an effective way forward in the quantitative analysis of EMG IP signal to assist the clinician in the diagnosis of neuromuscular disorders.

Action Potentials↗
PubMed2005

Load characterization and anomaly detection for voice over IP traffic.

We consider the problem of traffic anomaly detection in IP networks. Traffic anomalies typically arise when there is focused overload or when a network element fails and it is desired to infer these purely from the measured traffic. We derive new general formulae for the variance of the cumulative traffic over a fixed time interval and show how the derived analytical expression simplifies for the case of voice over IP traffic, the focus of this paper. To detect load anomalies, we show it is sufficient to consider cumulative traffic over relatively long intervals such as 5 min. We also propose simple anomaly detection tests including detection of over/underload. This approach substantially extends the current practice in IP network management where only the first-order statistics and fixed thresholds are used to identify abnormal behavior. We conclude with the application of the scheme to field data from an operational network.

Algorithms↗
PubMed1992

In vitro characterization of prostanoid FP-, DP-, IP- and TP-receptors on the non-pregnant human myometrium.

1. Prostaglandin F (PGF), PGD, PGI and thromboxane A2 (TXA2) receptors have been pharmacologically characterized on the non-pregnant human myometrium in vitro in accordance with the receptor classification proposed by Coleman et al. (1984). The tools for the classification include both natural prostanoids, synthetic, selective analogues and antagonists where available. 2. The potent excitatory actions of the natural FP-receptor prostanoid, PGF2 alpha, and the synthetic analogue, fluprostenol, indicate the presence of FP-receptors mediating contraction on the human myometrium. 3. PGD2 produced a biphasic response consisting of excitation followed by relaxation of spontaneous activity of the myometrium. The selective DP-receptor agonists, BW245C, produced purely inhibitory responses illustrating the presence of inhibitory DP-receptors in this tissue. The inhibitory responses of both PGD2 and BW245C were antagonized by the competitive DP-receptor antagonist, BWA 868C, providing conclusive evidence for the existence of DP-receptors. 4. PGI2 produced a biphasic response similar to PGD2. Iloprost, the EP1/IP-receptor agonist also produced a biphasic response, whilst the IP-receptor selective agonist, cicaprost, caused inhibition only, suggesting that inhibitory IP-receptors exist in the non-pregnant human myometrium. 5. The TXA2-mimetic, U46619, produced marked stimulation of the non-pregnant human myometrium and was approximately equipotent to PGF2 alpha and fluprostenol in this effect. The actions of U46619 were competitively antagonized by the TP-receptor antagonist GR32191 showing that excitatory TP-receptors exist in this tissue.6. All prostanoids tested, both natural and synthetic, had activity on the non-pregnant human myometrium in vitro, supporting the existence of a heterogeneous population of prostanoid receptors in this tissue. If the results from the present study are combined with those previously reported for EP-receptor agonists (Senior et al., 1991), it may be concluded that excitation may occur through FP-, TP-, EP3- and few EP,-receptors, whereas inhibition may occur through DP-, IP- and EP2-receptors.

Female↗
PubMed1999

Low-luminance visual stimuli compared with stroboscopic IPS in eliciting PPR in photosensitive patients.

PURPOSE: Photosensitivity is thought to play the most important role in the genesis of electronic screen games induced seizures (ESGIS). To elicit photoparoxysmal response (PPR) effectively, we performed EEG activation by low-luminance visual stimuli: 20 cd/m2 deep-red flicker and flickering 2 c/deg geometric pattern stimuli produced by strobofilters. We investigated efficacy of eliciting PPR by use of Grass PS33-plus stroboscopic 18-Hz intermittent photic stimulation (IPS) and low-luminance 18-Hz visual stimuli. METHODS: We studied 31 photosensitive patients. We gave stroboscopic IPS (eyes closed and eyes open); after deep-red flicker stimulation (eyes open), we gave flickering geometric-pattern stimuli by using dot, vertical grating, and horizontal grating patterns. RESULTS: Stroboscopic IPS elicited PPR in 14 patients, whereas absence of PPR provocation was found in 17 patients. Low-luminance visual stimuli elicited PPR in 30 patients, whereas absence of PPR provocation was found in only one patient. These PPR provocation differences in both stimuli were statistically significant (p < 0.001). CONCLUSIONS: The data suggest that low-luminance visual stimuli as described are useful for EEG diagnosis of ESGIS when seizures are thought to be due to photosensitivity.

Adolescent↗
PubMedDate not supplied

Chemoattractant factors (IP-10, MIP-1alpha, IL-16) mRNA expression in mononuclear cells from different tissues during acute SIVmac251 infection of macaques.

We have used semiquantitative RT-PCR to monitor the expression of mRNA encoding chemoattractant factors IP-10, MIP-1alpha, and IL-16 in freshly isolated peripheral blood mononuclear cells (PBMCs), lymph node mononuclear cells (LNMCs), and mononuclear cells obtained after bronchoalveolar lavages (BALMCs) of two cynomolgus macaques inoculated intravenously with a pathogenic isolate of simian immunodeficiency virus, SIVmac251. Concomitant with the peak of systemic viral replication (two weeks after experimental inoculation) and proinflammatory cytokine IL-6 mRNA expression, high levels of MIP-1alpha and IP-10 mRNA were produced in LNMCs and BALMCs. In BALMCs, in which we have reported a marked progressive overexpression of IFN-gamma mRNA coinciding with an increase in the CD8+ lymphocyte percentages, we noticed a progressive overexpression of IL-16 mRNA. Our results suggest the role of chemokines IP-10, MIP-1alpha, and IL-16 in the development of inflammatory and immune responses during the early stages of lentiviral infection.

Animals↗
PubMed1980

The adrenoceptor blocking properties of the new beta 2-selective antagonist, IPS 339 on tracheal smooth muscle and on slow contracting skeletal muscle.

The beta-adrenoceptor blocking properties of IPS 339 and propranolol were studied on isolated preparations of trachea and of the slow-contracting soleus muscle from the guinea-pig. Both compounds antagonized the relaxation of the trachea and the depression of subtetanic contractions of the soleus produced by the beta2-selective agonist, terbutaline. On the soleus muscle the pA2-values for IPS 339 and propranolol were similar and close to those obtained for propranolol on the trachea. However, on the trachea the slope of the Schildplot for IPS 339 against terbutaline became less than one and a reliable pA2-value could not be calculated.

Adrenergic beta-Antagonists↗
PubMed2001

Activation of IP(3)-protein kinase C-alpha signal transduction pathway precedes the changes of plasma cholesterol, hepatic lipid metabolism and induction of low-density lipoprotein receptor expression in 17-beta-oestradiol-treated rats.

The intracellular concentration of cholesterol is regulated by the balance between endogenous synthesis and exogenous uptake. Oestrogens have been reported to be involved in the physiological regulation of cellular cholesterol content. Relevant reports have focused on long-term responses and there is a lack of information about the relationship between the timing of the oestrogen effect and the regulation of cholesterol homeostasis. The aim of this work has been to set up a systematic picture of the short-term effects induced by oestrogen on hepatic lipid metabolism in vivo and the involvement of some relevant signal transduction pathways. At intervals after oestrogen administration (30 min to 6 h), oestrogen receptor expression and changes in liver cAMP, IP(3) and protein kinase C-alpha (PKC-alpha) were followed. Changes in the expression of the low density lipoprotein receptor at mRNA and protein levels, and of hydroxy-methyl-glutaryl-CoA reductase activity have been verified. At the same time, the content of hepatic cholesterol, ubiquinone and dolichol and of plasma cholesterol have been determined. Changes of rab 5 and rab 8, small GTP-binding prenylated proteins involved in the transfer of neosynthesised proteins through the cell, have been also checked. In vivo treatment with oestradiol produced no change in cyclic AMP but a rapid increase in IP(3), increased PKC-alpha localisation on the membranes and enhanced expression of the low density lipoprotein receptor in the liver occurred. PKC inhibition completely prevented any increase in low density lipoprotein receptor mRNA in isolated and perfused rat liver. Early changes of ubiquinone and dolichol content and a later reduction in hepatic hydroxy-methyl-glutaryl-CoA reductase activity and plasma cholesterol content were also detectable. A functional role of the IP(3) -protein kinase C-alpha pathway in the induction of the low density lipoprotein receptor is suggested. Experimental Physiology (2001) 86.1, 39-45.

Animals↗
PubMed2004

Prostaglandin receptors EP2, EP3, and IP mediate exudate formation in carrageenin-induced mouse pleurisy.

The roles of prostaglandins (PGs) as mediators of inflammation have been extensively studied, and production of PGI2 and PGE2 at inflammatory sites has been reported. However, it has not yet been clarified which type of PG receptors has a major role in inflammatory exudation. To examine in vivo role of PG receptors in inflammatory exudation, we induced pleurisy in PG receptors (IP, EP1, EP2, EP3, or EP4) knockout mice by intrapleural injection of carrageenin. Pleural exudate accumulation in wild-type (WT) mice at 1 to 5 h, but not at 24 h, was significantly attenuated by the pretreatment with indomethacin, indicating that PGs are responsible for exudate formation at the early phase of pleurisy. Pleural exudation at 1 to 5 h in IP, EP2, or EP3 knockout mice, but not in EP1 and EP4 knockout, was significantly reduced compared with in WT mice. In the exudates, 6-keto-PGF1alpha and PGE2 were detected as the major PGs, each with its peak concentration at 3 h. In addition, involvement of bradykinin in the phenomenon was suggested by the fact that captopril, a kininase inhibitor, enhanced the exudate formation and increased the amount of 6-keto-PGF1alpha and PGE2 and that a bradykinin B2-receptor antagonist inhibited the exudate formation. In contrast, leukocyte migration into pleural cavity was not influenced by indomethacin-treatment nor by these receptor deficiencies. These results demonstrate participation of EP2 and EP3 along with IP in pleural exudate formation but not in leukocyte migration in carrageenin-induced mouse pleurisy.

Alprostadil↗
PubMed1998

Selective activation of a chimeric Gi1/Gs G protein alpha subunit by the human IP prostanoid receptor: analysis using agonist stimulation of high affinity GTPase activity and [35S]guanosine-5'-O-(3-thio)triphosphate binding.

A FLAG-tagged form of the human IP prostanoid receptor was expressed stably in HEK 293 cells. This bound [3H]iloprost with high affinity and stimulated cAMP production when exposed to agonist. Iloprost produced weak stimulation of GTPase activity and [35S]guanosine-5'-O-(3-thio)triphosphate binding in membranes of these cells. Pretreatment of cells with pertussis toxin did not modify iloprost-mediated stimulation, but this was blocked by cholera toxin. The effects of iloprost were not increased by coexpression of either Gsalpha or Gi1alpha. In contrast, coexpression of a chimeric G protein alpha subunit in which the carboxyl-terminal six amino acids of Gi1alpha were altered to those of Gsalpha resulted in robust stimulation by iloprost. Because the chimeric G protein alpha subunit (Gi1/Gs6alpha) is not a substrate for either pertussis or cholera toxin, pretreatment of cells coexpressing the IP prostanoid receptor and Gi1/Gs6alpha with a mixture of these toxins resulted in resolution of the signal derived from activation of the chimeric G protein. Agonist-stimulated [35S]guanosine-5'-O-(3-thio)triphosphate binding and GTPase activity assays are the most commonly used strategies to examine interactions between G protein-coupled receptors and G proteins. These usually are not appropriate for receptors such as the IP prostanoid receptor that interact with G proteins with low rates of guanine nucleotide exchange and hydrolysis. Chimeric G proteins such as Gi1/Gs6alpha that allow appropriate receptor contacts to be converted to the higher nucleotide turnover rates typical of the Gi family G proteins can overcome this and offer a novel means to examine agonist function at such receptors.

Cell Line↗
PubMed2000

Induction of the chemokines interleukin-8 and IP-10 by human immunodeficiency virus type 1 tat in astrocytes.

A finding commonly observed in human immunodeficiency virus type 1 (HIV-1)-infected patients is invasion of the brain by activated T cells and infected macrophages, eventually leading to the development of neurological disorders and HIV-1-associated dementia. The recruitment of T cells and macrophages into the brain is likely the result of chemokine expression. Indeed, earlier studies revealed that levels of different chemokines were increased in the cerebrospinal fluid of HIV-1-infected patients whereas possible triggers and cellular sources for chemokine expression in the brain remain widely undefined. As previous studies indicated that HIV-1 Tat, the retroviral transactivator, is capable of inducing a variety of cellular genes, we investigated its capacity to induce production of chemokines in astrocytes. Herein, we demonstrate that HIV-1 Tat(72aa) is a potent inducer of MCP-1, interleukin-8 (IL-8), and IP-10 expression in astrocytes. Levels of induced IP-10 protein were sufficiently high to induce chemotaxis of peripheral blood lymphocytes. In addition, Tat(72aa) induced IL-8 expression in astrocytes. IL-8 mRNA induction was seen less then 1 h after Tat(72aa) stimulation, and levels remained elevated for up to 24 h, leading to IL-8 protein production. Tat(72aa)-mediated MCP-1 and IL-8 mRNA induction was susceptible to inhibition by the MEK1/2 inhibitor UO126 but was only modestly decreased by the inclusion of the p38 mitogen-activated protein kinase (MAPK) inhibitor SB202190. In contrast, Tat-mediated IP-10 mRNA induction was suppressed by SB202190 but not by the MEK1/2 inhibitor UO126. These findings indicate that MAPKs play a major role in Tat(72aa)-mediated chemokine induction in astrocytes.

Astrocytes↗
PubMed2001

Hantavirus infection induces the expression of RANTES and IP-10 without causing increased permeability in human lung microvascular endothelial cells.

Sin Nombre virus (SNV) and Hantaan virus (HTN) infect endothelial cells and are associated with different patterns of increased vascular permeability during human disease. It is thought that such patterns of increased vascular permeability are a consequence of endothelial activation and subsequent dysfunction mediated by differential immune responses to hantavirus infection. In this study, the ability of hantavirus to directly induce activation of human lung microvascular endothelial cells (HMVEC-Ls) was examined. No virus-specific modulation in the constitutive or cytokine-induced expression of cellular adhesion molecules (CD40, CD54, CD61, CD62E, CD62P, CD106, and major histocompatibility complex classes I and II) or in cytokines and chemokines (eotaxin, tumor necrosis factor alpha, interleukin 1beta [IL-1beta], IL-6, IL-8, MCP-1, MIP-1alpha, and MIP-1beta) was detected at either the protein or message level in hantavirus-infected HMVEC-Ls. Furthermore, no virus-specific enhancement of paracellular or transcellular permeability or changes in the organization and distribution of endothelial intercellular junctional proteins was observed. However, infection with either HTN or SNV resulted in detectable levels of the chemokines RANTES and IP-10 (the 10-kDa interferon-inducible protein) in HMVEC-Ls within 72 h and was associated with nuclear translocation of interferon regulatory factor 3 (IRF-3) and IRF-7. Gamma interferon (IFN-gamma)-induced expression of RANTES and IP-10 could also be detected in uninfected HMVEC-Ls and was associated with nuclear translocation of IRF-1 and IRF-3. Treatment of hantavirus-infected HMVEC-Ls with IFN-gamma for 24 h resulted in a synergistic enhancement in the expression of both RANTES and IP-10 and was associated with nuclear translocation of IRF-1, IRF-3, IRF-7, and NF-kappaB p65. These results reveal a possible mechanism by which hantavirus infection and a TH1 immune response can cooperate to synergistically enhance chemokine expression by HMVEC-Ls and trigger immune-mediated increases in vascular permeability.

Animals↗
PubMed1999

Ceramide triggers intracellular calcium release via the IP(3) receptor in Xenopus laevis oocytes.

Ceramide, a product of sphingomyelin turnover, is a lipid second messenger that mediates diverse signaling pathways, including those leading to cell cycle arrest and differentiation. The mechanism(s) by which ceramide signals downstream events have not been fully elucidated. Here we show that, in Xenopus laevis oocytes, ceramide-induced maturation is associated with the release of intracellular calcium stores. Ceramide caused a dose-dependent elevation in the second messenger inositol 1,4,5-trisphosphate (IP(3)) via activation of G(q/11)alpha and phospholipase C-betaX. Elevation of IP(3), in turn, activated the IP(3) receptor calcium release channel on the endoplasmic reticulum, resulting in a rise in cytoplasmic calcium. Thus our study demonstrates that cross talk between the ceramide and phosphoinositide signaling pathways modulates intracellular calcium homeostasis.

Animals↗
PubMed2001

Role of IP(3) in modulation of spontaneous activity in pacemaker cells of rabbit urethra.

Isolated interstitial ("pacemaker") cells from rabbit urethra were examined using the perforated-patch technique. Under voltage clamp at -60 mV, these cells fired large spontaneous transient inward currents (STICs), averaging -860 pA and >1 s in duration, which could account for urethral pacemaker activity. Spontaneous transient outward currents (STOCs) were also observed and fell into two categories, "fast" (<100 ms in duration) and "slow" (>1 s in duration). The latter were coupled to STICs, suggesting that they shared the same mechanism, while the former occurred independently at faster rates. All of these currents were abolished by cyclopiazonic acid, caffeine, or ryanodine, suggesting that they were activated by Ca(2+) release. When D-myo-inositol 1,4,5-trisphosphate (IP(3))-sensitive stores were blocked with 2-aminoethoxydiphenyl borate, the STICs and slow STOCs were abolished, but the fast STOCs remained. In contrast, the fast STOCs were more nifedipine sensitive than the STICs or the slow STOCs. These results suggest that while fast STOCs are mediated by a mechanism similar to STOCs in smooth muscle, STICs and slow STOCs are driven by IP(3). These results support the hypothesis that pacemaker activity in the urethra is driven by the IP(3)-sensitive store.

Animals↗
PubMed2002

Localization of IP in rabbit kidney and functional role of the PGI(2)/IP system in cortical collecting duct.

To clarify the role of the PGI(2)/PGI(2) receptor (IP) system in rabbit cortical collecting duct (RCCD), we characterized the expression of IP receptors in the rabbit kidney. We show by Northern and Western blotting that IP mRNA and protein was detectable in all three regions of the kidney. To determine how PGI(2) signals, we compared the effects of different PGI(2) analogs [iloprost (ILP), carba-prostacyclin (c-PGI(2)), and cicaprost (CCP)] in the isolated perfused RCCD. PGI(2) analogs did not increase water flow (L(p)). Although PGI(2) analogs did not reduce an established L(p) response to 8-chlorophenylthio-cAMP, they equipotently inhibited AVP-stimulated L(p) by 45%. The inhibitory effect of ILP and c-PGI(2) on AVP-stimulated L(p) is partially reversed by the protein kinase C inhibitor staurosporine and abolished by pertussis toxin; no effect was obtained with CCP. In fura 2-loaded RCCD, CCP did not alter cytosolic Ca(2+) concentration ([Ca(2+)](i)), but, in the presence of CCP, individual infusion of ILP and PGE(2) increased [Ca(2+)](i), suggesting that CCP did not cause desensitization to either ILP or PGE(2). We concluded that ILP and c-PGI(2) activate PKC and the liberation of [Ca(2+)](i) but not CCP. This suggested an important role for phosphatidylinositol hydrolysis in mediating ILP and c-PGI(2) effects but not CCP in RCCD.

Algorithms↗
PubMed2005

Adenovirus-directed ocular innate immunity: the role of conjunctival defensin-like chemokines (IP-10, I-TAC) and phagocytic human defensin-alpha.

PURPOSE: Adenovirus (Ad), a major cause of viral conjunctivitis worldwide, is controlled initially by the innate immune response on the ocular surface. In the present study, cultured human conjunctival epithelial cells were used to identify host genes responsive to infection by a clinical isolate of Ad5, and the antiviral activity of some of their peptide products was investigated. METHODS: Primary human conjunctival epithelial cells in culture were infected with Ad5 at high (1.0), low (0.1), or zero (0.0) multiplicities of infection (MOI) and harvested at different times after infection (1.5, 6, and 16 hours). Host gene expression was profiled with oligonucleotide microarrays (GeneChips; Affymetrix, Santa Clara, CA). Peptide products of interest were tested for antiviral activity in direct inhibition assays against respiratory serotypes (Ad3, Ad5), ocular serotypes (Ad8, Ad19), and HSV-1. RESULTS: At high MOI, viral infection suppressed the interferon (IFN)-mediated host antiviral response seen at low MOI. At 16 hours after infection, 63 unique characterized transcripts were identified that were robustly and significantly suppressed by high MOI, (i.e., MOI [0.1]/MOI [0.1] > or = 2, P < 0.006). Of these, 29 (46%) transcripts are involved in IFN signaling or are IFN or virus induced. This subset included CXCL10 and CXCL11, encoding IP-10 and I-TAC, respectively. These defensin-like chemokines and human alpha-defensin-1 directly inhibited Ad3 and Ad5 but not Ad8 or Ad19. CONCLUSIONS: In response to low-level Ad5 infection, conjunctival epithelial cells showed upregulation of IFN-associated genes. The peptide products of two of these, IP-10 and I-TAC, are directly active against Ad3, and IP-10 is active against Ad5. The ocular tropism of Ad8 and Ad19 may be due in part to their resistance to these defensin-like chemokines.

Adenoviruses, Human↗
PubMed2004

Antimitogenic effects of HDL and APOE mediated by Cox-2-dependent IP activation.

HDL and its associated apo, APOE, inhibit S-phase entry of murine aortic smooth muscle cells. We report here that the antimitogenic effect of APOE maps to the N-terminal receptor-binding domain, that APOE and its N-terminal domain inhibit activation of the cyclin A promoter, and that these effects involve both pocket protein-dependent and independent pathways. These antimitogenic effects closely resemble those seen in response to activation of the prostacyclin receptor IP. Indeed, we found that HDL and APOE suppress aortic smooth muscle cell cycle progression by stimulating Cox-2 expression, leading to prostacyclin synthesis and an IP-dependent inhibition of the cyclin A gene. Similar results were detected in human aortic smooth muscle cells and in vivo using mice overexpressing APOE. Our results identify the Cox-2 gene as a target of APOE signaling, link HDL and APOE to IP action, and describe a potential new basis for the cardioprotective effect of HDL and APOE.

Animals↗