NF-?B translocation and endothelial cell activation is potentiated by macrophage-released signals co-secreted with TNF-? and IL-1?

López-Bojórquez, Lucia Nikolaia; Arechavaleta-Velásco, Fabián; Vadillo-Ortega, Felipe; Montes-Sánchez, Delina G.; Ventura-Gallegos, José Luis; Zentella‐Dehesa, Alejandro

doi:10.1007/s00011-004-1297-6

Cited by 28 publications

(23 citation statements)

References 32 publications

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“…NF-ĸB activation is generally measured by the rapid degradation of intracellular IĸB on the administration of a suitable stimulus [49,50]. There are two main forms of IĸB in the endothelium – namely IĸBα and IĸBβ.…”

Section: Resultsmentioning

confidence: 99%

Estradiol Modulates Tumor Necrosis Factor-Induced Endothelial Inflammation: Role of Tumor Necrosis Factor Receptor 2

Chakrabarti¹,

Davidge²

2012

J Vasc Res

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The sex hormone estradiol (E₂) appears to mediate both anti-atherogenic and pro-inflammatory effects in premenopausal women, suggesting a complex immunomodulatory role. Tumor necrosis factor (TNF) is a key pro-inflammatory cytokine involved in the pathogenesis of atherosclerosis and other inflammatory diseases. Alterations at the TNF receptors (TNFRs) and their downstream signaling/transcriptional pathways can affect inflammatory responses. Given this background, we hypothesized that chronic E₂ exposure would alter endothelial inflammatory response involving modulation at the levels of TNFRs and signaling pathways. HUVECs were used as the model system. Pre-treatment with E₂ did not significantly alter TNF-induced upregulation of pro-inflammatory molecules ICAM-1 (3–6 times) and VCAM-1 (5–7 times). However, pharmacological inhibition of transcriptional pathways suggested a partial shift from NF-ĸB (from 97 to 64%) towards the JNK/AP-1 pathway in ICAM-1 upregulation on E₂ treatment. In contrast, VCAM-1 expression remained NF-ĸB dependent in both control (∼96%) and E₂ treated (∼85%) cells. The pro-inflammatory TNF effects were mediated by TNFR1. Interestingly, E₂ pre-treatment increased TNFR2 levels in these cells. Concomitant TNFR2 activation (but not TNFR1 activation alone) led to the shift towards JNK/AP-1-mediated ICAM-1 upregulation in E₂-treated cells, suggesting the effects of chronic E₂ to be dependent on TNFR2 signaling.

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Section: Resultsmentioning

confidence: 99%

Estradiol Modulates Tumor Necrosis Factor-Induced Endothelial Inflammation: Role of Tumor Necrosis Factor Receptor 2

Chakrabarti¹,

Davidge²

2012

J Vasc Res

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“…Nuclear proteins were obtained as previously described (20). In brief, untreated fish (control) or fish treated with MMI only or MMI plus either T3 or 3,5-T2 (30 nM) for 5 days were killed, and the livers were resuspended 1:10 (wt/vol) in a hypotonic buffer (10 mM HEPES, pH 7.9, 10 mM KCl, 1 mM EDTA, 5 mM DTT).…”

Section: Methodsmentioning

confidence: 99%

3,5-Diiodothyronine in vivo maintains euthyroidal expression of type 2 iodothyronine deiodinase, growth hormone, and thyroid hormone receptor β1 in the killifish

Garcı́a-G¹,

López-Bojórquez²,

Núñez³

et al. 2007

American Journal of Physiology-Regulatory, Integrative and Comp

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Until recently,3, has been considered an inactive by-product of triiodothyronine (T3) deiodination. However, studies from several laboratories have shown that 3,5-T2 has specific, nongenomic effects on mitochondrial oxidative capacity and respiration rate that are distinct from those due to T3. Nevertheless, little is known about the putative genomic effects of 3,5-T2. We have previously shown that hyperthyroidism induced by supraphysiological doses of 3,5-T2 inhibits hepatic iodothyronine deiodinase type 2 (D2) activity and lowers mRNA levels in the killifish in the same manner as T3 and T4, suggesting a pretranslational effect of 3,5-T2 (Garcia-G C, Jeziorski MC, Valverde-R C, Orozco A. Gen Comp Endocrinol 135: 201-209, 2004). The question remains as to whether 3,5-T2 would have effects under conditions similar to those that are physiological for T3. To this end, intact killifish were rendered hypothyroid by administering methimazole. Groups of hypothyroid animals simultaneously received 30 nM of either T3, reverse T3, or 3,5-T2. Under these conditions, we expected that, if it were bioactive, 3,5-T2 would mimic T3 and thus reverse the compensatory upregulation of D2 and tyroid receptor ␤1 and downregulation of growth hormone that characterize hypothyroidism. Our results demonstrate that 3,5-T2 is indeed bioactive, reversing both hepatic D2 and growth hormone responses during a hypothyroidal state. Furthermore, we observed that 3,5-T2 and T3 recruit two distinct populations of transcription factors to typical palindromic and DR4 thyroid hormone response elements. Taken together, these results add further evidence to support the notion that 3,5-T 2 is a bioactive iodothyronine. deiodinase type 2; thyroid hormone receptor ␤1; thyroid hormone response element; killifish IODOTHYRONINES OR THYROID hormones (TH) are essential in regulating energy expenditure and development. Triiodothyronine (T 3 ) is the bioactive TH, which modulates gene expression in virtually every vertebrate tissue through ligand-dependent transcription factors, the TH receptors (TR). Sequential deiodination of thyroxine (T 4 ) generates T 3 as well as other iodothyronines that have been considered inactive by-products, but, recently, interest has grown in identifying bioactive iodothyronines in addition to T 4 and T 3 . Studies from several laboratories have suggested that 3,5-diiodothyronine (3,5-T 2 ), a putative product of the deiodination pathway involved in T 3 metabolism, could be a peripheral mediator of some effects of TH on mitochondrial oxidative capacity and respiration rate. To date, results in mammals suggest that 3,5-T 2 has specific actions on oxygen consumption that are distinct from those of T 3 : they are not attenuated by inhibition of protein synthesis and are more rapid than those due to T 3 (for review, see Ref. 12). Genomic effects of 3,5-T 2 have been analyzed in only a few classic iodothyronine-dependent genes, such as thyroid stimulating hormone (TSH), thyroid receptor ␤2 (TR␤2), iodothyronine deiodinase type 1 (D1)...

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“…Hepes, pH·7.9, 10·mmol·l -1 KCl, 1·mmol·l -1 EDTA, 5·mmol·l -1 DTT) as previously described (López-Bojórquez et al, 2004). The tissue was broken mechanically with a plastic homogenizer at low velocity.…”

Section: Nuclear and Cytoplasmic Extractsmentioning

confidence: 99%

Functional identification of an osmotic response element (ORE) in the promoter region of the killifish deiodinase 2 gene (FhDio2)

López-Bojórquez

Villalobos

Garcı́a-G

et al. 2007

Journal of Experimental Biology

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SUMMARY The physiological role played by thyroid hormones (TH) in hydro-osmotic homeostasis in fish remains a controversial issue. Previous studies have shown that in Fundulus heteroclitus (killifish) hypo-osmotic stress increases liver iodothyronine deiodinase type 2 (D2) mRNA and D2 activity. In this study we identified two conserved osmotic response element (ORE) motifs in the promoter region of the killifish D2 gene (FhDio2) and examined their possible role in the transcriptional regulation of FhDio2during hypo-osmotic stress. As assessed by the electrophoretic mobility shift assay, results from in vivo and in vitro experiments demonstrate that exposure to an abrupt hyposmotic challenge triggers in the liver of killifish a strong nuclear recruitment of a putative osmotic response element binding protein (OREBP). This protein–DNA binding is time-dependent, attains a maximum within 2–8 h after the osmotic stress,and is followed by a significant increase in D2 activity. Furthermore,protein–DNA binding and the subsequent elevation in enzyme activity were blocked by the tyrosine kinase inhibitor genistein. Thus, during hypo-osmotic stress, a putative OREBP kinase-activated pathway stimulates FhDio2transcription and enzymatic activity. These data and the fact that D2 is the major enzyme providing local intracellular T3 suggest that TH plays a direct role in osmoregulation in fish, possibly by participating in hepatic ammonia metabolism. This study provides important insight into the physiological role of TH in hydro-osmotic homeostasis in fish.

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NF-?B translocation and endothelial cell activation is potentiated by macrophage-released signals co-secreted with TNF-? and IL-1?

Abstract: The above results suggest that the physiological context of factors co-secreted by LPS-activated macrophages enhances TNF-alpha mediated endothelial activation.

Cited by 28 publications

References 32 publications

Estradiol Modulates Tumor Necrosis Factor-Induced Endothelial Inflammation: Role of Tumor Necrosis Factor Receptor 2

Estradiol Modulates Tumor Necrosis Factor-Induced Endothelial Inflammation: Role of Tumor Necrosis Factor Receptor 2

3,5-Diiodothyronine in vivo maintains euthyroidal expression of type 2 iodothyronine deiodinase, growth hormone, and thyroid hormone receptor β1 in the killifish

Functional identification of an osmotic response element (ORE) in the promoter region of the killifish deiodinase 2 gene (FhDio2)

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