Regulatory peptides
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Regulatory peptides · Feb 2010
Meprin-alpha metalloproteases enhance lipopolysaccharide-stimulated production of tumour necrosis factor-alpha and interleukin-1beta in peripheral blood mononuclear cells via activation of NF-kappaB.
Lipopolysaccharide (LPS) induces the expression of a wide range of pro-inflammatory mediators via NF-kappaB activation. These pro-inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta), may be important in triggering atherogenesis. We have previously observed that actinonin, a meprin inhibitor, suppressed the formation of atherosclerotic plaques and, in in vitro experiments, actinonin also had an effect on the way LPS altered THP-1 cell function. ⋯ Our results show that LPS-induced IL-1beta and TNF-alpha production by PBMCs was significantly reversed by meprin-alpha specific siRNA. In addition, the augmentation of meprin-alpha of the LPS-induced expression of TNF-alpha and IL-1beta was significantly decreased by Bay-117082, an inhibitor of NF-kappaB. In conclusion, our data indicate that meprin-alpha is capable of increasing LPS-induced production of cytokines in peripheral blood mononuclear cells, which might be associated with the activation of NF-kappaB.
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Regulatory peptides · Jan 2010
Angiotensin II activates JAK2/STAT3 pathway and induces interleukin-6 production in cultured rat brainstem astrocytes.
We have shown that tyrosine kinases and mitogen-activated protein kinases mediate angiotensin II (Ang II) effects in cultured rat astrocytes. In this study, we investigated whether Ang II induces Janus kinase (JAK) 2, signal transducer and activators of transcription (STAT) 3 phosphorylation, and interleukin-6 (IL-6) secretion in cultured brainstem rat astrocytes. Ang II increased JAK2 phosphorylation in a time- and dose-dependent manner. ⋯ Our study showed for the first time that Ang II induced JAK2/STAT3 phosphorylation and IL-6 secretion through activation of the Ang II AT(1) receptor in brainstem astrocytes. In addition, Ang II stimulated IL-6 secretion and astrocyte growth through the JAK2 pathway in brainstem astrocytes. These results provide new insights into pro-inflammatory and mitogenic signaling mechanisms of Ang II in astrocytes.
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Regulatory peptides · Jun 2009
Effects of galanin-monoaminergic interactions on vasopressin secretion in rat neurohypophyseal cell cultures.
The effects of dopamine (DA), serotonin (5-HT), histamine (HA), adrenaline (ADR), noradrenaline (NADR) and K(+) administration on vasopressin (VP) secretion were studied in 13-14-day cultures of rat neurohypophyseal (NH) cells, and it was examined whether galanin (GAL) can modify the VP release enhancement induced by these monoaminergic compounds. An enzymatic dissociation technique was used to make the rat NH cell cultures. The VP contents of the supernatants of 14-day cultures were determined by radioimmunoassay. ⋯ GAL had no effect on the VP level increase induced by K(+), which causes a non-specific hormone secretion. The results indicate that the changes in VP secretion induced by the monoaminergic system can be directly influenced by the GAL-ergic system. The interactions between the monoaminergic and GAL-ergic systems regarding VP secretion occur at the level of the posterior pituitary.
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Regulatory peptides · Nov 2008
Venous endotelin-1 (ET-1) and brain natriuretic peptide (BNP) plasma levels during 6-month bosentan treatment for pulmonary arterial hypertension.
Bosentan, an endothelin (ET) ETA-ETB receptors antagonist, is an effective therapy for idiopathic pulmonary arterial hypertension (PAH) and for PAH related to connective tissue disease (CTD). The aim of this study was to evaluate the behaviour of ET-1 and brain natriuretic peptide (BNP) venous plasma levels during a 6-month dual ET-1 receptor blockade and the potential influence of baseline ET-1 venous plasma levels on the clinical efficacy of bosentan. ⋯ Our data confirm that bosentan is an effective therapy for patients with PAH. Its clinical efficacy (effort tolerance and NYHA) seems to be independent from baseline venous ET1 plasma levels. Bosentan therapy seems to elicit different patterns in ET-1 and BNP plasma levels, with decrease of the peptides only in patients with higher activation of the systemic endothelin system. Further studies are warranted to explore the potential impact of baseline ET-1 levels on the long-term effects (clinical worsening) of bosentan therapy.
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Regulatory peptides · Oct 2008
Effects of sucrose, glucose and fructose on peripheral and central appetite signals.
In the Western world, consumption of soft drinks has increased the last three decades and is partly responsible for the epidemic-like increase in obesity. Soft drinks, originally sweetened by sucrose, are now sweetened by other caloric sweeteners, such as fructose. In this study, we investigated the short-term effect of sucrose, glucose or fructose solutions on food intake and body weight in rats, and on peripheral and central appetite signals. ⋯ Hypothalamic POMC mRNA was down-regulated in rats receiving glucose or fructose. In conclusion, consumption of glucose, sucrose or fructose solution results in caloric overconsumption and body weight gain through activation of hunger signals and depression of satiety signals as well as activation of reward components. The weight-promoting effect of these sugar solutions may possibly be ameliorated by the down-regulation of NPY mRNA and increased serum leptin.