The p160 nuclear receptor co-activator RAC3 exerts an anti-apoptotic role through a cytoplasmatic action.

The p160 nuclear receptor co-activators represent a family of molecules, which are recruited by steroid nuclear receptors as well as other transcription factors that are overexpressed in several tumors. We investigated the role of one member of this family on the sensitivity of cells to apoptosis. We observed that overexpression of the RAC3 (receptor-associated co-activator-3) p160 co-activator inhibits hydrogen peroxide-induced cell death in human embryonic kidney 293 (HEK293) cells.

TNF-alpha enhances estrogen-induced cell proliferation of estrogen-dependent breast tumor cells through a complex containing nuclear factor-kappa B.

Breast tumors are usually classified according to their response to estrogens as hormone-dependent or -independent. In this work, we investigated the role of the proinflammatory cytokine TNF-alpha on the estrogen-receptor-positive T47D breast ductal tumor cells. We have found that TNF-alpha exerts a mitogenic effect, inducing cyclin D1 expression and activation of the transcription factor NF-kappaB.

[Different enzymatic activities recruitment by specific domains of TIF2 are involved in NF-kappaB transactivation].

We have previously shown that nuclear receptor coactivator overexpression significantly enhanced NF-kappaB activity in a dose response manner. We studied the mechanism by which TIF2 regulates NF-kappaB activity. We determined that: 1) the p38 specific inhibitor reduces 50% NF-kappaB transcriptional activity, even in cells that overexpress distinct TIF2 deletions; 2) there is a physical interaction between TIF2 and p38 and RelA determined through in vitro translated protein binding assays; 3) TIF2 is a p38 substrate; 4) there is a physical interaction between TIF2 and IKK in TNF-alpha 20 ng/ml stimulated or not HEK 293 cell protein extract, and IkappaB only in basal conditions, determined by binding pull down assays.

Control of dendritic cell differentiation by angiotensin II.

Here we analyze the role of the angiotensinergic system in the differentiation of dendritic cells (DC). We found that human monocytes produce angiotensin II (AII) and express AT1 and AT2 receptors for AII. DC differentiated from human monocytes in the presence of AT1 receptor antagonists losartan or candesartan show very low levels of CD1a expression and poor endocytic and allostimulatory activities.

Angiotensin II and the transcription factor Rel/NF-kappaB link environmental water shortage with memory improvement.

One of the essential requirements even in the most ancient life forms is to be able to preserve body fluid medium. In line with such requirement, animals need to perform different behaviors to cope with water shortages. As angiotensin II (ANGII) is involved on a widespread range of functions in vertebrates, including memory modulation, an integrative role, in response to an environmental water shortage, has been envisioned.

Nonpeptide antagonists of AT1 receptor for angiotensin II delay the onset of acute respiratory distress syndrome.

We have previously reported that losartan, a selective antagonist of AT1 receptors for angiotensin II (AII), strongly suppresses the activation of neutrophils by N-formylmethionyl-leucyl-phenylalanine (fMLP) through a mechanism that does not involve inhibition of AT1 receptors. Herein, we analyze whether losartan would prevent the development of the acute respiratory distress syndrome (ARDS) triggered by lung bacterial infection. We found that losartan (0.

Losartan, a selective inhibitor of subtype AT1 receptors for angiotensin II, inhibits neutrophil recruitment in the lung triggered by fMLP.

We have shown that losartan, a selective inhibitor of AT1 receptors for angiotensin II (AII), inhibits the binding of [3H]fMLP to neutrophil receptors (FPR). Here, we analyze, in Wistar rats, the effect of losartan on neutrophil recruitment in the lung triggered by fMLP. We found that i.

High environmental salinity induces memory enhancement and increases levels of brain angiotensin-like peptides in the crab Chasmagnathus granulatus.

Previous work on the brackish-water crab Chasmagnathus granulatus demonstrated that an endogenous peptide similar to angiotensin II plays a significant role in enhancing long-term memory that involves an association between context and an iterative danger stimulus (context-signal memory). The present results show that this memory enhancement could be produced by moving crabs from brackish water to sea water (33.0%) and keeping them there for at least 4 days.

The Th1 and Th2 cytokines IFN-gamma and IL-4 antagonize the inhibition of monocyte IL-1 receptor antagonist by glucocorticoids: involvement of IL-1.

Monocytes express IL-1 and IL-1 receptor antagonist (IL-1Ra) in response to lipopolysaccharide (LPS). IL-1 self-induction contributes to the increase in IL-1 following LPS stimulation. LPS-stimulated IL-1 and IL-1Ra production are inhibited by glucocorticoids.

Angiotensin II (3-8) induces long-term memory improvement in the crab Chasmagnathus.

A shadow moving overhead acts as a danger stimulus and elicits an escape response in the crab Chasmagnathus that habituates after 15 trials and for a long period of time. Previous work showed that angiotensin II enhances this long-term memory. Present results indicate: (1) that the facilitatory effect of angiotensin II is not blocked by either losartan, DUP 753 or the Parke Davis compound PD 123177; (2) that the angiotensin II (3-8) fragment has an enhancing effect on crab's memory stronger than that reported for the integer octopeptide; (3) that the hypermnestic effect of angiotensin II (3-8) is dose-dependent and saralasin reversible.

Losartan, a selective inhibitor of subtype AT1 receptors for angiotensin II, inhibits the binding of N-formylmethionyl-leucyl-phenylalanine to neutrophil receptors.

Losartan, a selective antagonist of AT1 receptors for angiotensin II, is widely used clinically to manage hypertension. We report here that losartan markedly inhibits neutrophil shape change, adherence and chemiluminescence responses triggered by N-formylmethionyl-leucyl-phenylalanine (fMLP), without affecting responses induced by immune complexes, zymosan or concanavalin A. Neither saralasin, another antagonist of angiotensin II receptors, nor captopril, an angiotensin-converting enzyme inhibitor, reproduced the effects of losartan.

Molecular and functional evidence for in vitro cytokine enhancement of human and murine target cell sensitivity to glucocorticoids. TNF-alpha priming increases glucocorticoid inhibition of TNF-alpha-induced cytotoxicity/apoptosis.

Cytokine-induced glucocorticoid secretion and glucocorticoid inhibition of cytokine synthesis and pleiotropic actions act as important safeguards in preventing cytokine overreaction. We found that TNF-alpha increased glucocorticoid-induced transcriptional activity of the glucocorticoid receptor (GR) via the glucocorticoid response elements (GRE) in L-929 mouse fibroblasts transfected with a glucocorticoid-inducible reporter plasmid. In addition, TNF-alpha also enhanced GR number.

Glucocorticoids inhibit the autoregulatory induction of interleukin-1 in monocytes after endotoxin stimulation.

Interleukin-1 (IL-1) is an important mediator in the mechanisms underlying the immune and inflammatory responses. It has pleiotropic effects in host defense and, when present in high concentrations, participates in the development of pathological processes. IL-1 is the most potent cytokine in the activation of the hypothalamic-pituitary-adrenal axis during infection and therefore leads to a glucocorticoid increase.

Angiotensin II enhances long-term memory in the crab Chasmagnathus.

An opaque screen moving overhead provokes an escape response in the crab Chasmagnathus granulatus that habituates after a few presentations of the eliciting stimulus. Fifteen trials with a 180-s intertrial interval or 30 trials with a 90-s interval (strong training protocol) ensures long-term habituation (LTH) of the response for 24 h, whereas 10 trials (weak training protocol) fail to induce it. However, robust LTH is obtained when crabs are injected with human angiotensin (All; 50 pmol) immediately after a weak training protocol.

Thyrotropin-releasing hormone hyperactivity in the preoptic area of spontaneously hypertensive rats.

Thyrotropin-releasing hormone (TRH) plays an important role in central cardiovascular regulation through the activation of different neurotransmitter systems at distinct extrahypothalamic sites. To study possible alterations in the TRH system in the hypertensive state, we measured TRH concentration in cerebrospinal fluid and TRH content of the preoptic area in spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY) by radioimmunoassay. In addition, we also measured the density of the TRH receptor in this area by a rapid filtration technique using [3H]methyl-TRH.

TRH receptor on immune cells: in vitro and in vivo stimulation of human lymphocyte and rat splenocyte DNA synthesis by TRH.

This work examined whether (1) immune cells express thyrotrophin releasing hormone (TRH) receptor mRNA and (2) TRH modulates lymphocyte activation. By Northern blot of RNA extracted from human peripheral blood mononuclear cells (PBMC) and rat splenocytes, a single TRH receptor mRNA band of about 3.8 kb (identical to that obtained from pituitary cells) was obtained, under both basal and stimulated conditions.

Acute administration of angiotensin II improves long-term habituation in the crab Chasmagnathus.

A shadow moving overhead acts as a danger stimulus and elicits an escape response in the crab Chasmagnathus granulatus that habituates after 15 trials and for a long period. A shorter training of ten trials fails to induce long-term habituation; however, a good retention of the habituated response is manifest after a 24-h interval when angiotensin II (AII) (10(-6) M, 3 ng/g) is injected post-training. By contrast, no amnestic effect of AII was found even though high doses were administered.

Sensitivity of human peripheral blood mononuclear leukocytes to visible light.

Overnight light exposure of cultured human peripheral blood mononuclear leukocytes [PBML], significantly increased basal [3H]thymidine incorporation and upon stimulation with phytohemagglutinin [PHA]. Melatonin (10(-9) to 10(-5) M) enhanced the light-induced increase of [3H]thymidine incorporation, while serotonin (10(-9) to 10(-7) M) stimulated [3H]thymidine incorporation in the dark. The wavelengths responsible of this effect were restricted to the blue-green zone of the spectrum.

Cultured peripheral blood mononuclear leukocytes from anorexia nervosa patients are refractory to visible light.

Cultured human peripheral blood mononuclear leukocytes [PBML] from patients with anorexia nervosa [AN] did not respond to light stimulation as PBML of normal controls [NC] did. During winter, visible light increased [3H]thymidine incorporation into DNA of NC-PBML stimulated with phytohemagglutinin [PHA]. This effect was enhanced by 10(-7) M melatonin.

Synenkephalin processing in embryonic rat brain.

Synenkephalin (proenkephalin 1-70) is produced and secreted as an intact molecule or as a part of precursors in the adult brain and adrenal medulla, respectively. However, it is cleaved to low molecular weight peptides in proliferating immune cells. Considering that the pre-proenkephalin gene is expressed in the embryonic rat brain during the cell proliferation stage, we studied the processing of synenkephalin in embryonic rat brains (E18) and compared it with the processing in adult rat brains.

Superinduction of mitogen-stimulated interferon-gamma production and other lymphokines by Sendai virus.

We observed that Sendai virus preinduction of peripheral blood mononuclear cells and subsequent mitogenic stimulation resulted in: (i) Superproduction of interferon-gamma, (IFN-gamma) (ii) an increase in interleukin-2 (IL-2) synthesis that correlates with DNA synthesis when stimulated with phytohemagglutinin (PHA) or pokeweed mitogen (PWM) after treatment with the Sendai virus, while stimulation with Protein A from Staphylococcus aureus was not affected, and (iii) enhanced tumor necrosis factor-alpha (TNF-alpha) production in response to bacterial lipopolysaccharide (LPS). Treatment of monocyte cultures with LPS and cycloheximide or actinomycin-D inhibited the superinduction phenomenon. When cycloheximide was added at the viral induction time, the inhibition of TNF-alpha superproduction and DNA synthesis was still observed.

Low lymphocyte interferon-gamma production and variable proliferative response in anorexia nervosa patients.

Interferon-gamma (IFN-gamma) production by peripheral blood mononuclear cells (PBMC) in 14 patients with anorexia nervosa (AN) was significantly lower than in 14 age-matched healthy controls. Follow-up samples in four patients displayed low levels, except in two when they recovered the IFN-gamma production as the hormonal cycles were restored. A large interindividual variation for the lymphocyte proliferative response was observed in 30 AN patients.

Differential posttranslational processing of proenkephalin in rat bone marrow and spleen mononuclear cells: evidence for synenkephalin cleavage.

Proenkephalin (PENK) messenger RNA was reported to be present in bone marrow mononuclear cells (BMMC) and spleen mononuclear cells (SMC). Nevertheless, the pattern of PENK products in normal cells of the rat immune system, which is important for defining the physiological role of PENK gene expression, has not been well established. In this work we have characterized the processing of the opioid portion (met-enkephalin-containing peptides) and nonopioid portion (synenkephalin-derived peptides) of PENK in rat BMMC and SMC.

Early complete maturation of proenkephalin processing induced by dexamethasone in the adrenal gland of neonatal rats.

We have previously found that proenkephalin processing is incomplete in the neonatal rat adrenal medulla and have postulated that immaturity of either the nervous input to the gland or the endocrine hypothalamus-pituitary-adrenal axis might be involved in the failure of the gland to yield free met-enkephalin. Therefore, we investigated whether cholinergic and glucocorticoid agonists may act in vivo on neonatal proenkephalin processing; reserpine, a strong activator of precursor cleavage, was also tested. Acute administration of nicotine, pilocarpine and reserpine to 24-hour-old rats increased the content of enkephalin-containing peptides (ECP) after 72 h (4-day-old rats) and activated the posttranslational processing of proenkephalin to high, intermediate and low molecular weight peptides respectively, although free met-enkephalin was not produced.