共查询到20条相似文献,搜索用时 15 毫秒
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Incubation of rat hepatocytes in primary culture with IL-1beta at a concentration of 2.5 units/ml resulted in an increase (+80%) in the amount of apoE mRNA without any effect upon apoE synthesis. IL-6 at a low concentration (10 units/ml) induced a decrease (-35%) in the amount of apoE mRNA, but increased apoE synthesis (+28%). No effect was observed with higher concentrations of IL-1beta (10 units/ml) or IL-6 (100 units/ml). These results suggest that inflammatory cytokines IL-1beta and IL-6 modulate the expression of apoE gene in cultured rat hepatocytes, at a concentration that does not induce the acute phase response. 相似文献
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Prostaglandin E2 regulates macrophage-derived tumor necrosis factor gene expression 总被引:42,自引:0,他引:42
S L Kunkel M Spengler M A May R Spengler J Larrick D Remick 《The Journal of biological chemistry》1988,263(11):5380-5384
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W Gu G E Rice G D Thorburn 《Prostaglandins, leukotrienes, and essential fatty acids》1990,40(1):27-30
Prostaglandin E2 (PGE2) and F2 alpha (PGF2 alpha) produced by 15 days pregnant rat myometrium, by parturient rat myometrium and myometrium plus endometrium were measured in vitro. The results showed that the PGs produced by parturient myometrium were higher than these obtained during mid-pregnancy. Myometrium with endometrium released more PGs than myometrium alone, and the addition of arachidonic acid (AA) at 10 DM did not show any significant effect. Exogenous progesterone or estradiol-17b at a concentration of 1 Dmol had no effect on parturient uterine PG secretions. 相似文献
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Cheon H Rho YH Choi SJ Lee YH Song GG Sohn J Won NH Ji JD 《Journal of immunology (Baltimore, Md. : 1950)》2006,177(2):1092-1100
In inflamed joints of rheumatoid arthritis, PGE(2) is highly expressed, and IL-10 and IL-6 are also abundant. PGE(2) is a well-known activator of the cAMP signaling pathway, and there is functional cross-talk between cAMP signaling and the Jak-STAT signaling pathway. In this study, we evaluated the modulating effect of PGE(2) on STAT signaling and its biological function induced by IL-10 and IL-6, and elucidated its mechanism in THP-1 cells. STAT phosphorylation was determined by Western blot, and gene expression was analyzed using real-time PCR. Pretreatment with PGE(2) significantly augmented IL-10-induced STAT3 and STAT1 phosphorylation, as well as suppressors of cytokine signaling 3 (SOCS3) and IL-1R antagonist gene expression. In contrast, PGE(2) suppressed IL-6-induced phosphorylation of STAT3 and STAT1. These PGE(2)-induced modulating effects were largely reversed by actinomycin D. Pretreatment with dibutyryl cAMP augmented IL-10-induced, but did not change IL-6-induced STAT3 phosphorylation. Misoprostol, an EP2/3/4 agonist, and butaprost, an EP2 agonist, augmented IL-10-induced STAT3 phosphorylation and SOCS3 gene expression, but sulprostone, an EP1/3 agonist, had no effect. H89, a protein kinase A inhibitor, and LY294002, a PI3K inhibitor, diminished PGE(2)-mediated augmentation of IL-10-induced STAT3 phosphorylation. In this study, we found that PGE(2) selectively regulates cytokine signaling via increased intracellular cAMP levels and de novo gene expression, and these modulating effects may be mediated through EP2 or EP4 receptors. PGE(2) may modulate immune responses by alteration of cytokine signaling in THP-1 cells. 相似文献
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Prostaglandin E2 levels and human periodontal disease 总被引:8,自引:0,他引:8
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Sp1 represses IL-2 receptor alpha chain gene expression 总被引:7,自引:0,他引:7
Sp1 is a DNA-binding protein that acts as a positive regulator of eukaryotic gene expression. The interleukin-2 receptor alpha chain (IL2R alpha) gene 5' regulatory region contains a single Sp1 consensus motif that overlaps a CArG box capable of binding serum response factor (SRF). The CArG box has previously been shown to be important for IL2R alpha gene expression. In this study, the results of competition experiments suggest that Sp1 and SRF compete for binding to the CArG region. Site-directed mutagenesis and transient transfection assays indicate that the IL2R alpha gene Sp1 serves the unusual role of repressing gene expression, most likely by competing for binding of nuclear factor(s) to the CArG box. 相似文献
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Daines MO Tabata Y Walker BA Chen W Warrier MR Basu S Hershey GK 《Journal of immunology (Baltimore, Md. : 1950)》2006,176(12):7495-7501
IL-13, a critical cytokine for allergic inflammation, exerts its effects through a complex receptor system including IL-4Ralpha, IL-13Ralpha1, and IL-13Ralpha2. IL-4Ralpha and IL-13Ralpha1 form a heterodimeric signaling receptor for IL-13. In contrast, IL-13Ralpha2 binds IL-13 with high affinity but does not signal. IL-13Ralpha2 exists on the cell surface, intracellularly, and in soluble form, but no information is available regarding the relative distributions of IL-13Ralpha2 among these compartments, whether the compartments communicate, and how the relative expression levels impact IL-13 responses. Herein, we investigated the distribution of IL-13Ralpha2 in transfected and primary cells, and we evaluated how the total level of IL-13Ralpha2 expression impacted its distribution. Our results demonstrate that the distribution of IL-13Ralpha2 is independent of the overall level of expression. The majority of the IL-13Ralpha2 protein existed in intracellular pools. Surface IL-13Ralpha2 was continually released into the medium in a soluble form, yet surface expression remained constant supporting receptor trafficking to the cell surface. IL-13Ralpha2 inhibited IL-13 signaling proportionally to its level of expression, and this inhibition could be overcome with high concentrations of IL-13. 相似文献
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Stéphane Dragon Lianyu Shan F. Estelle Simons Abdelilah S. Gounni 《Biochemical and biophysical research communications》2009,384(2):167-4442
Interleukin (IL)-9 is associated with key pathological features of asthma such as airway hyperresponsiveness, bronchoconstriction and mucus production. Inflammatory responses mediated by IL-9 rely on the expression of the IL-9R which has been reported on lung epithelial cells, T lymphocytes and recently on airway granulocyte infiltrates. In this study, we assessed the regulatory and constitutive cell surface expression of the IL-9Rα in unfractionated and purified human neutrophils from atopic asthmatics, atopic non-asthmatics and healthy normal controls. We demonstrate that TH2 cytokines (IL-4 or IL-13) and granulocyte macrophage-colony stimulating factor (GM-CSF) up-regulated mRNA and cell surface expression levels of the IL-9Rα in primary human and HL-60 differentiated neutrophils. Pharmacological inhibition of NF-κB did not affect TH2-mediated IL-9Rα expression in human neutrophils although IFN-γ and IL-10 down-regulated IL-9Rα expression when co-incubated with IL-4, IL-13 or GM-CSF. Collectively, our results reveal a regulatory function for IFN-γ and IL-10 on modulating the inducible IL-9Rα expression levels on peripheral blood neutrophils by TH2 cytokines. 相似文献
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Prostaglandin E2-bisphosphonate conjugates: potential agents for treatment of osteoporosis. 总被引:2,自引:0,他引:2
L Gil Y Han E E Opas G A Rodan R Ruel J G Seedor P C Tyler R N Young 《Bioorganic & medicinal chemistry》1999,7(5):901-919
Conjugates of bisphosphonates (potential bone resorption inhibitors) and prostaglandin E2 (a bone formation enhancer) were prepared and evaluated for their ability to bind to bone and to liberate, enzymatically, free PGE2. The conjugate 3, an amide at C-1 of PGE2 proved to be too stable in vivo while conjugate 6, a thioester, was too labile. Several PGE2, C-15 ester-linked conjugates (18, 23, 24 and 31) were prepared and conjugate 23 was found to bind effectively to bone in vitro and in vivo and to liberate PGE2 at an acceptable rate. A 4-week study in a rat model of osteoporosis showed that 23 was better tolerated and more effective as a bone growth stimulant than daily maximum tolerated doses of free PGE2. 相似文献
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A Gayá O de la Calle J Yagüe E Alsinet M D Fernández M Romero V Fabregat J Martorell J Vives 《Journal of immunology (Baltimore, Md. : 1950)》1991,146(12):4209-4214
There is growing evidence to suggest a regulatory role of IL-4 in the immune system affecting both proliferation and lymphokine production. In the present work we have analyzed the effect of IL-4 on IL-2 and IFN-gamma synthesis by stimulating CD4+ human T cells (+10% accessory cells) with Con A in the presence of several doses (1 to 100 U/ml) of human rIL-4. The results showed an impaired IL-2 and IFN-gamma synthesis in the presence of IL-4. This inhibition was dose dependent and was evident only when IL-4 was added in the first 2 h of culture. Moreover, the external addition of IL-2 did not revert the inhibitory effect of IL-4 on IL-2 and IFN-gamma synthesis induced by Con A. We have also analyzed the effect of IL-4 on the expression of both alpha- and beta-chains of the IL-2R. Although the expression of IL-2R alpha mRNA was not modified after 6 h in culture in the presence of IL-4, a decrease was observed at 24 and 48 h. The addition of rIL-2 showed that the inhibition in IL-2R alpha expression could be explained by an impairment in the up-regulatory signal transmitted through the IL-2R. In addition to this, IL-4 did not modify the IL-2R beta mRNA expression at 6 and 24 h although a decreased expression was observed at 48 h which could be explained by the defective IL-2 production. The differential effect of IL-4 on the up-regulatory effect of IL-2 in the expression of IL-2R alpha and IL-2R beta suggest the existence of different regulatory mechanisms acting on the expression of both chains. 相似文献
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In the isolated perfused rat heart, the dose-related cardiostimulation produced by norepinephrine (NE) or calcium chloride (Ca2+) was followed by a corresponding increase in coronary flow (CF) and in the cardiac level of adenosine 3',5'-cyclic phosphate (cAMP). Prolonged prostaglandin E2 (pge2) infusion did not change the basic force of contraction, CF, or cAMP level but when NE or Ca2+ were administered, only the responses of the CF and the cAMP were diminished. A phosphodiesterase inhibitor, diazoxide (Dx), caused insignificant increase in the basal cAMP, without affecting the force of contraction or CF. With NE or Ca2+, during Dx both the changes in CF and cAMP were augmented compared to the nontreated hearts. The inhibitory effects of NE or Ca2+ remained unchanged. Propranolol abolished the NE but not the Ca2+ effects. It is suggested that PGE2 modulates the cardiac cAMP level and that the latter plays an important role in the adaptive regulation of the CF. It is also postulated that changes in cAMP levels may be brought about by the hyperactivity per se produced by a variety of cardiostimulating agents. 相似文献
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Prostaglandin E2 promotes IL-4-induced IgE and IgG1 synthesis 总被引:3,自引:0,他引:3
R L Roper D H Conrad D M Brown G L Warner R P Phipps 《Journal of immunology (Baltimore, Md. : 1950)》1990,145(8):2644-2651
PG of the E series are generally known to suppress immune responses, however, we have found that PGE synergizes with IL-4 to induce IgE and IgG1 production in LPS-stimulated murine B lymphocytes. PGE2 and PGE1 (10(-6) to 10(-8) M) significantly increase IgE and IgG1 production (up to 26-fold) at all concentrations of IL-4 tested. In addition to its effects on IgE and IgG1, PGE also causes a significant decrease in IgM and IgG3 synthesis, suggesting that PGE may promote IL-4-induced class switching. The specificity of the E series PG effect is demonstrated by the fact that PGF2 alpha (10(-6) M) does not alter production of any of these isotypes. Because PGE can mediate its effects through cAMP in some cases, we investigated the importance of cAMP levels in regulation of isotype expression. Other agents that increase intracellular cAMP levels (cholera toxin and dibutyryl cAMP) were assessed for their ability to regulate isotype differentiation. Cholera toxin (100 pg/ml) and dibutyryl cAMP (100 microM) significantly enhanced IgE and IgG1 production and diminished IgM and IgG3 synthesis. We also show that PGE and cholera toxin elevate intracellular cAMP in B lymphocytes in a dose-dependent manner. In contrast, PGF2 alpha (10(-6) M) and the B subunit of cholera toxin (100 pg/ml) did not increase cAMP and did not regulate the isotype of Ig produced, reiterating the importance of cAMP in enhancing isotype differentiation. Although PGE is known to inhibit a number of immune responses, our data show that it is not always inhibitory. PGE may play a role in atopy in vivo where PGE-secreting cells such as macrophages, follicular dendritic cells, and fibroblasts can promote IgE synthesis. This research emphasizes the importance of PGE in regulation of the humoral immune response and adds a new stimulatory action to the repertoire of known PGE effects. 相似文献
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IL-7R alpha gene expression is inversely correlated with cell cycle progression in IL-7-stimulated T lymphocytes 总被引:2,自引:0,他引:2
Swainson L Verhoeyen E Cosset FL Taylor N 《Journal of immunology (Baltimore, Md. : 1950)》2006,176(11):6702-6708
IL-7 plays a major role in T lymphocyte homeostasis and has been proposed as an immune adjuvant for lymphopenic patients. This prospect is based, at least in part, on the short-term expansion of peripheral T cells in rIL7-treated mice and primates. Nevertheless, in vivo, following initial increases in T cell proliferation and numbers, lymphocytes return to a quiescent state. As the bases for this cell cycle exit have not yet been elucidated, it is important to assess the long-term biological effects of IL-7 on quiescent human T lymphocyte subsets. In this study, we find that IL-7-stimulated CD4+ naive lymphocytes enter into cell cycle with significantly delayed kinetics as compared with the memory population. Importantly though, these lymphocytes exit from the cell cycle despite the continuous replenishment of rIL-7. This response is distinct in memory and naive CD4+ lymphocytes with memory cells starting to exit from cycle by day 10 vs day 18 for naive cells. Return to quiescence is associated with a cessation in IL-7R signaling as demonstrated by an abrogation of STAT-5 phosphorylation, despite an up-regulation of surface IL-7Ralpha. Indeed, an initial 10-fold decrease in IL-7Ralpha mRNA levels is followed by increased IL-7Ralpha expression in naive as well as memory T cells, with kinetics paralleling cell cycle exit. Altogether, our data demonstrate that IL-7 promotes the extended survival of both naive and memory CD4+ T cells, whereas cycling of these two subsets is distinct and transient. Thus, IL-7 therapy should be designed to allow optimal responsiveness of naive and memory T cell subsets. 相似文献
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J Marcinkiewicz W Radziszewski B M Chain 《Folia histochemica et cytobiologica / Polish Academy of Sciences, Polish Histochemical and Cytochemical Society》1992,30(1):1-4
Eicosanoids are important mediators of inflammation, and have been shown to have potent, and usually suppressive immunoregulatory activities. In the paper, we have examined the role of prostaglandin (PGE2) production in the regulation of two cytokines, IL-2 and IL-3, which both play a key role in contact sensitivity and delayed type hypersensitivity reactions. In agreement with previous studies, we demonstrate that prostaglandins down-regulate IL-2 production in the system. Unexpectedly, however, IL-3 levels are enhanced in the presence of the prostaglandin PGE2 and conversely, are inhibited by treatment with aspirin, a potent inhibitor of prostaglandin metabolism. The implications of this result in terms of the immunoregulatory role of PGs will be discussed. 相似文献