Peptides
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Randomized Controlled Trial
Effects of corticotropin-releasing hormone on proopiomelanocortin derivatives and monocytic HLA-DR expression in patients with septic shock.
Little is known about interactions between immune and neuro-endocrine systems in patients with septic shock. We therefore evaluated whether the corticotropin-releasing hormone (CRH) and/or proopiomelanocortin (POMC) derivatives [ACTH, β-endorphin (β-END), β-lipotropin (β-LPH), α-melanocyte stimulating hormone (α-MSH) or N-acetyl-β-END (Nac-β-END)] have any influences on monocyte deactivation as a major factor of immunosuppression under septic shock conditions. Sixteen patients with septic shock were enrolled in a double-blind, cross-over and placebo controlled clinical study; 0.5μg/(kgbodyweighth) CRH (or placebo) were intravenously administered for 24h. ⋯ Additionally, a significant increase of mHLA-DR expression was observed 16h after starting the CRH infusion; 8h later, the mHLA-DR expression had decreased again. Our results indicate that the up-regulation of mHLA-DR expression after CRH infusion is not dependent on the release of POMC derivatives. From the correlation between plasma concentration of α-MSH and mHLA-DR expression, we conclude that in patients with septic shock the down-regulation of mHAL-DR expression is accompanied by the loss of monocytic release of α-MSH into the cardiovascular compartment.
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Ghrelin acts on the growth hormone secretagogue receptor (GHSR) in the brain to elicit changes in physiological functions. It is associated with the neural control of appetite and metabolism, however central ghrelin also affects fertility. Central ghrelin injection in rats suppresses luteinizing hormone (LH) concentrations and pulse frequency. ⋯ We also observed no coexpression of GHSR-eGFP and RFamide-related peptide-3 (RFRP3) neurons in the dorsomedial hypothalamic nucleus. Importantly, we observed that approximately half of the GHSR-eGFP cells in the AVPV coexpressed Ghsr mRNA (as determined by in situ hybridization) so these data should be interpreted accordingly. Although ghrelin influences the hypothalamic reproductive axis, our data using a GHSR-eGFP reporter suggests ghrelin regulates neurons expressing ERα but does not directly act on GnRH, kisspeptin, TH, or RFRP3 neurons, as little or no GHSR-eGFP coexpression was observed.
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Intestinal injury significantly contributes to critical illness, sepsis and multiorgan failure. TFF2 (Trefoil Factor 2) is expressed and secreted preferentially by gastric mucous neck cells. TFF2 gene expression is promptly increased after gut injury, and its expression profile broadens to include the regenerative epithelia of virtually the entire gastrointestinal tract. ⋯ Analysis of TFF2 levels dynamics revealed that TFF2 levels kept steady state during the 5-day period. Significantly higher levels of TFF2 were in patients with Multiple Organ Dysfunction Syndrome (MODS). The difference was noticed also in ROC analysis.
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Apelin is a newly discovered peptide that has been recently shown to have cardioprotective effects in the animal model of myocardial infarction (MI) and ischemia/reperfusion (I/R) injuries. The aim of the present study was to investigate the long term cardioprotective effect of [Pyr1]-apelin-13 in the rat model of MI. Male Wistar rats (n=22) were randomly divided into three groups: (1) sham operated group (2) control MI group and (3) MI treated with apelin (MI-AP group). ⋯ Myocardial infarct size (IS) and hemodynamic function were also measured at the end of the study at day 14. We found out that post infarct treatment with apelin decreases infarct size, serum levels of LDH, CK-MB and MDA and increases heart rate and serum level of NO in the consecutive days, but there were no significant differences in blood pressure in the MI-AP group in comparison with MI. In conclusion, apelin has long term cardioprotective effects against myocardial infarction through attenuation of cardiac tissue injury and lipid peroxidation and enhancement of NO production.
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Cultured bovine adrenal chromaffin cells (BCCs) are employed to study first messenger-specific signaling by cytokines and neurotransmitters occurring in the adrenal medulla following immune-related stress responses. Here, we show that the cytokine TNF-alpha, and the neuropeptide transmitter PACAP, acting through the TNFR2 and PAC1 receptors, activate distinct signaling pathways, with correspondingly distinct transcriptomic signatures in chromaffin cells. We have carried out a comprehensive integrated transcriptome analysis of TNF-alpha and PACAP gene regulation in BCCs using two microarray platforms to maximize transcript identification. ⋯ Distinct groups of transcription factors potentially controlling the expression of TNF-alpha or PACAP-responsive genes were found: most of the genes up-regulated by TNF-alpha contained transcription factor binding sites for members of the Rel transcription factor family, suggesting TNF-alpha-TNFR2 signaling occurs mainly through the NF-KB signaling pathway. Surprisingly, EGR1 was predicted to be the primary transcription factor controlling PACAP-modulated genes, suggesting PACAP signaling to the nucleus occurs predominantly through ERK, rather than CREB activation. Comparison of TNFR2-dependent versus TNFR1-dependent gene induction, and EGR1-mediated transcriptional activation, may provide a pharmacological avenue to the unique pathways activated by the first messengers TNF-alpha and PACAP in neuronal and endocrine cells.