Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P01189 (beta-endorphin)
 21,003 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Since the time of Freud, psychiatry has embraced the proposition that physiological and/or psychological stress precipitates various psychiatric disorders. To this effect, we propose that a continuum of liability obtains between stress, anxiety states and anorexia nervosa--a continuum which is grounded on a cytokine profile common to each of these conditions. For example, the biological response to stress, anxiety states and anorexia nervosa includes the elevation of interleukin-1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF-alpha), and downregulation of interferon-gamma (IFN-gamma). Sustained elevation of IL-1 beta and TNF-alpha dysregulates both somatostatin and insulin secretion, the latter of which influences regional cerebral blood flow (rCBF) and brain energy metabolism. In addition, IL-1 beta and TNF-alpha influence the expression of certain crucial neuropeptides, which are known to be associated with anxiety states and anorexia nervosa. These neuropeptides include: beta-endorphin, cholecystokinin (CCK), neuropeptide Y (NPY) and vasoactive intestinal peptide (VIP). beta-endorphin effects glucose metabolism in the limbic system, CCK increases the release of beta-endorphin from the anterior pituitary, NPY is a powerful anxiolytic that regulates beta-endorphin and insulin, while VIP indirectly regulates the expression of TNF-alpha through the inhibition of interleukin-4 (IL-4).
 ...
PMID:Tumor necrosis factor-alpha: is there a continuum of liability between stress, anxiety states and anorexia nervosa? 1034 Feb 96

The present study was designed to determine whether the glucocorticoid inhibitory feedback mechanism plays a role in the well-known tolerance of the neuroendocrine-immune axis response to repeated endotoxemia. Adult male rats underwent adrenalectomy (ADX) and were implanted with a subcutaneous corticosterone (compound B, CB, 75 mg) pellet, or sham operated and implanted with a placebo pellet. On the morning of day 8 after surgery (experimental day, D1), all rats received an intravenous injection of lipopolysaccharide (LPS) (25 microg/kg body weight) which was repeated daily until D5. Blood was drawn via intravenous indwelling catheters before (sample time zero) as well as 1, 2, 3 and 4 h after LPS treatment on D1, 3 and 5 for measurements of corticotropin (ACTH), CB, tumor necrosis factor-alpha (TNF-alpha) and leptin. In sham animals, tolerance to repeated LPS administration was complete by D5 for the corticotrope axis and the immune response. In addition, LPS was found to stimulate leptin secretion on day 1 in intact rats, an effect that also disappeared thereafter. ADX + CB rats showed only a partial tolerance of the corticotrope axis on D5, whereas tolerance of the immune response was similar to that found in sham animals. Interestingly, the acute stimulation of leptin secretion by LPS in ADX + CB rats was qualitatively similar to that of intact controls on D1, but plasma leptin levels were significantly reduced on D3 and 5 compared to controls. Our results demonstrate that the adrenal response tolerance of the hypothalamo-pituitary-adrenal axis to repeated endotoxemia. In addition, our finding that TNF-alpha secretion follows the same pattern in sham-operated and in adrenalectomized animals suggests that unlike the corticotrope axis, tolerance of the immune response does not depend upon stimulated CB levels. The decrease in circulating levels of leptin following ADX is consistent with the stimulatory effects of glucocorticoids on leptin secretion. However, our finding of an acute stimulation of leptin secretion by LPS in ADX + CB animals demonstrates that this effect of endotoxemia is at least partially glucocorticoid independent.
 ...
PMID:Role of glucocorticoids in the response of the hypothalamo-corticotrope, immune and adipose systems to repeated endotoxin administration. 1034 77

The cytokine and neuroendocrine host responses to experimental challenge with lipopolysaccharide (LPS) were studied in human immunodeficiency virus (HIV)-infected subjects and uninfected control subjects. Elevations in circulating concentrations of tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, and IL-8 were significantly greater in HIV-infected subjects than control subjects after LPS challenge. All subjects showed a significant increase in circulating concentrations of adrenocorticotropin, cortisol, and norepinephrine after LPS challenge, but there was not a significant difference between the responses of these hormones in the HIV-infected and -uninfected subjects. Compared with the control subjects, the HIV-infected subjects had a significantly reduced IL-10 response and a reduced IL-1 receptor antagonist response. It is concluded that the TNF-alpha, IL-6, IL-8, and IL-10 cytokine responses to LPS in vivo are disrupted in HIV subjects but that this is not related to disruption of the hypothalamo-pituitary-adrenal axis.
 ...
PMID:In vivo cytokine and neuroendocrine responses to endotoxin in human immunodeficiency virus-infected subjects. 1035 68

The role of endogenous interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha) in modulating the hypothalamic-pituitary-adrenal (HPA) axis response was examined in male C57BL/6 mice injected with endotoxin (lipopolysaccharide, LPS) or saline at 24-hour intervals for 4 or 8 consecutive days. The mice were divided into four groups: (1) LPS injections for 4 or 8 days and LPS injection on day 5 or 9, respectively (LPS-LPS); (2) LPS injections for 4 or 8 days and saline injection on day 5 or 9, respectively (LPS-saline); (3) saline injections for 4 or 8 days and LPS injection on day 5 or 9, respectively (saline-LPS), and (4) saline injections for 4 or 8 days and saline injection on day 5 or 9 (saline-saline). The mice were sacrificed by decapitation 2 h after the last injection and plasma levels of hormones and cytokines and tissue levels of IL-1beta were measured. Plasma adrenocorticotropin (ACTH) levels were significantly attenuated in the LPS-LPS group compared with the dramatic increases in the saline-LPS group following 4 or 8 days of endotoxin treatment. Plasma corticosterone concentrations were comparable in the LPS-LPS group after 4 days' treatment, but significantly lower following 8 days of treatment when compared with saline-LPS group. Repeated endotoxin treatment followed by a single saline injection (LPS-saline) did not alter the levels of IL-1beta in plasma or any of the tissues examined. IL-1beta levels in the hippocampus, hypothalamus, adrenal gland and plasma were elevated to comparable levels in the saline-LPS and LPS-LPS groups after 4 days of treatment. In contrast to the plasma IL-1beta response, TNFalpha levels were dramatically increased in the saline-LPS group but not in the LPS-LPS group following the 4-day treatment regimen. Increases in IL-1beta concentrations were seen in all tissues following one endotoxin challenge in the saline-LPS group following the 8-day treatment regimen, while increases were significantly attenuated in the hypothalamus, adrenal gland and plasma in LPS-LPS for 8 days. The sustained increases in tissue levels of IL-1beta following 4-day endotoxin treatment appears to have functional consequences since [125I]IL-1alpha binding was significantly decreased in the LPS-saline group compared with the saline-saline group. Furthermore, [125I]IL-1alpha binding was markedly reduced in the LPS-LPS group compared with the saline-LPS group. There was a significant positive correlation between plasma ACTH and IL-1beta after a single and repeated LPS treatment for 4 days, while a significant correlation was seen between plasma ACTH and TNFalpha following one but not repeated LPS treatment. These data demonstrate a differential regulation of IL-1beta and TNFalpha by repeated endotoxin treatment and suggest that while TNFalpha may be important modulating the attenuated pituitary adrenocortical response following the 4-day endotoxin treatment, IL-1beta appears to be the primary regulator of the response following the 8-day endotoxin treatment in the regulation of the HPA axis.
 ...
PMID:Differential effects of one and repeated endotoxin treatment on pituitary- adrenocortical hormones in the mouse: role of interleukin-1 and tumor necrosis factor-alpha. 1039 14

Borna disease virus (BDV) replicates in brain cells. The neonatally infected rat with BDV exhibits developmental-neuromorphological abnormalities, neuronal cytolysis, and multiple behavioral and physiological alterations. Here, we report on the levels of interleukin-1beta (IL-1beta), IL-1 receptor antagonist (IL-1Ra), tumor necrosis factor-alpha (TNF-alpha), transforming growth factor-beta1 (TGF-beta1), IL-1 receptor type I (IL-1RI), IL-1 receptor accessory protein (IL-1R AcP) I and II, glycoprotein 130, and various neuropeptide mRNAs in the cerebellum, parieto-frontal cortex, hippocampus and hypothalamus of BDV-infected rats at 7 and 28 days postintracerebral BDV inoculation. The data show that cytokine and neuropeptide mRNA components are abnormal and differentially modulated in brain regions. IL-1beta, TNF-alpha and TGF-beta1 mRNA levels were up-regulated in all brain regions following BDV inoculation. The same cerebellar samples from BDV-infected animals exhibited the highest levels of IL-1beta, IL-1Ra, TNF-alpha, IL-1RI, and IL-1R AcP II mRNA expression. The profiles of IL-1beta, IL-1Ra, TNF-alpha, and TGF-beta1 mRNA induction in the cerebellar samples were highly intercorrelated, indicating an association among cytokine ligand mRNAs. Cytokine mRNA induction was differentially up-regulated among brain regions, except for TGF-beta1. Specificity of transcriptional changes in response to BDV infection is also suggested by the up-regulation of cytokine and neuropeptide Y mRNAs associated with down-regulation of pro-opiomelanocortin, and with no change of IL-1R AcPI, dynorphin and leptin receptor mRNAs in the same brain region samples. Other data also show a differential mRNA component modulation in distinct brain regions obtained from the same rats depending on the stage of BDV infection. The conclusion of these studies is that cytokines may play a role in the neuropathophysiology of neonatally BDV-infected rats.
 ...
PMID:Persistent Borna disease virus infection of neonatal rats causes brain regional changes of mRNAs for cytokines, cytokine receptor components and neuropeptides. 1048 22

Alpha-melanocyte-stimulating hormone is produced by several different cell types including neural cells, endothelial cells, monocytes, and keratinocytes. A biologic role in melanocyte pigmentation is widely recognized, but more recent studies describe a part in modulating inflammatory and immune responses. The aim of the this study was to investigate the mechanism by which alpha-melanocyte-stimulating hormone antagonizes proinflammatory cytokine action. We report that alpha-melanocyte-stimulating hormone (10-9 M) was effective in opposing a tumor necrosis factor-alpha stimulated increase in NF-kappaB DNA binding activity in: (i) normal ocular melanocytes; (ii) cells cultured from ocular melanoma tumors; and (iii) two cutaneous melanoma cell lines. NF-kappaB is activated by many inflammatory mediators and controls transcription of genes required for immune and inflammatory responses. The transcription factor complex was positively identified as the p50/p65 heterodimer, recognized to have transcriptional activating potential. Maximum reduction of NF-kappaB DNA binding activity with alpha-melanocyte-stimulating hormone was detected 2 h after cellular stimulation and varied from between 53% and 18% depending on cell type. Whereas the acute inhibitory effects could be mimicked by elevating cyclic adenosine monophosphate, alpha-melanocyte-stimulating hormone was not found to have any effect on the relative level of IkappaBalpha protein expression over 24 h. These data show that alpha-melanocyte-stimulating hormone has a pronounced effect on NF-kappaB activity in melanocytes and melanoma cells, identifying a specific dimeric complex, and suggest this to be a key pathway by which immunomodulation/anti-inflammation may operate. The results may also be considered in the broader context of general inflammatory pathologies concerning cells which express alpha-melanocyte-stimulating hormone receptors and utilize the NF-kappaB signaling pathway.
 ...
PMID:Alpha-melanocyte-stimulating hormone inhibits NF-kappaB activation in human melanocytes and melanoma cells. 1050 41

Lipopolysaccharide (LPS) is known to stimulate the synthesis and secretion of various proinflammatory cytokines in both the peripheral immune cells and the brain. Yet, the relative contribution of peripheral and central cytokines to the LPS-induced activation of the hypothalamo-pituitary-adrenal axis is still poorly understood. In this study, utilizing the push-pull perfusion technique of the rat brain, we attempted to characterize in detail the temporal profiles of interleukin (IL)-1beta, IL-6, and tumor necrosis factor (TNF)-alpha after intravenous (i.v.) or intraperitoneal (i.p.) administration of LPS in both the general circulation and the hypothalamic paraventricular nucleus (PVN), which is the primary source of corticotropin releasing hormone (CRH). Temporal changes in plasma adrenocorticotropic hormone (ACTH) and CRH levels in the PVN were also monitored. We collected blood and perfusates every 30 min from 11:00 to 17:00 h. At 12:00 h, 1.0 or 2.5 mg/kg body weight of LPS was given via an i.v. or i.p. route, respectively. Peak ACTH response occurred 30 min after i.v. LPS and 1.5 h after ip LPS. Of the three cytokines measured in the plasma, TNF-alpha showed the fastest rise in synchrony with peak ACTH secretion after both i.v. and i.p. LPS. Although plasma IL-6 also showed a robust rise, its peak level occurred later than the ACTH peak. Elevation of plasma IL-1beta was the smallest among the three cytokines. CRH levels in the PVN reached their peaks 1 and 2.5 h after the ACTH peak following i.p. and i.v. LPS, respectively. Irrespective of the route of LPS administration, IL-6 and TNF-alpha levels in the PVN showed significant rises 1-2 h after the ACTH peak, but IL-1beta in the PVN did not significantly change during the entire period of observation. The results of the present study suggest that circulating TNF-alpha may play the most important role in triggering the early, peak phase of ACTH secretion after both i.v. and i.p. LPS. Although it is possible that brain TNF-alpha, IL-6, and circulating IL-6, may be involved in the later, protracted phase of ACTH secretion induced by LPS, IL-1beta in both the brain and peripheral circulation seems to play the smallest role in ACTH secretion. This is the first study to characterize the LPS-induced temporal changes in IL-1beta, IL-6, and TNF-alpha in both plasma and PVN simultaneously in conscious, freely moving rats.
 ...
PMID:Temporal profiles of interleukin-1beta, interleukin-6, and tumor necrosis factor-alpha in the plasma and hypothalamic paraventricular nucleus after intravenous or intraperitoneal administration of lipopolysaccharide in the rat: estimation by push-pull perfusion. 1058 Jul 40

Overwhelming inflammatory immune response can result in systemic inflammation and septic shock. To prevent excessive and deleterious action of proinflammatory cytokines after they have produced their initial beneficial effects, the immune system can release several anti-inflammatory mediators, including interleukin-10, interleukin-1 receptor antagonist, and soluble tumor necrosis factor receptors, thus initiating a compensatory anti-inflammatory response syndrome. However, in vivo the delicate balance between pro- and anti-inflammatory responses is additionally controlled by the central nervous system. Therefore, proinflammatory cytokines stimulate the hypothalamic-pituitary-adrenal axis and enhance sympathetic nerve system activity. The mediators of these neuroimmune pathways can again suppress immune cell functions to control systemic inflammation. The question is, however, what happens if the immunoinhibitory CNS pathways are activated without systemic inflammation? This can result from production of cytokines in the brain following infection, injury, or ischemia or in response to various stressors (e.g., life events, depression, anxiety) or directly from brainstem irritation. The answer is that this may generate a brain-mediated immunodepression. Many animal and clinical studies have demonstrated a stress and brain cytokine mediated decrease in the cellular immune response at the lymphocyte level. More recently, the importance of monocytes in systemic immunocapacity has been shown. Monocytic inactivation with decreased capability of antigen presentation and depressed secretion of proinflammatory cytokines increases the risk of infectious complications. Interestingly, cytokines in the brain and other stressors can also generate systemic immunodepression at the monocyte level. In this scenario the catecholamine-induced release of the potent anti-inflammatory cytokine interleukin-10 is a newly discovered mechanism of the brain-mediated monocyte deactivation in addition to the "well known" immunosuppressive action of glucocorticoids. Furthermore, other neuropeptides such as alpha-melanocyte-stimulating hormone and beta-endorphin which can be released in stressful situations have also inhibitory effects on immune cells. Thus mediators of the CNS are implicated in the regulation of immune functions and may play a role in both conditioning the host's response to endogenous or exogenous stimuli and generating a "brain-mediated" immunodepression.
 ...
PMID:Mechanisms of brain-mediated systemic anti-inflammatory syndrome causing immunodepression. 1061 37

Certain functional interactions between the nervous, endocrine, and immune systems are mediated by cytokines. The pro-inflammatory cytokines, interleukin-1 (IL-1) and tumor necrosis factor (TNF) were among the first to be recognized in this regard. A modulator of these cytokines, IL-10, has been shown to have a wide range of activities in the immune system; in this review, we describe its production and actions in the hypothalamic-pituitary-adrenal (HPA) axis. IL-10 is produced in pituitary, hypothalamic, and neural tissues in addition to lymphocytes. IL-10 enhances corticotropin releasing factor (CRF) and corticotropin (ACTH) production in hypothalamic and pituitary tissues, respectively. Further downstream in the HPA axis endogenous IL-10 has the potential to contribute to regulation of glucocorticosteroid production both tonically and following stressors. Our studies and those of others reviewed here indicate that IL-10 may be an important endogenous regulator in HPA axis activity and in CNS pathologies such as multiple sclerosis. Thus, in addition to its more widely recognized role in immunity, IL-10's neuroendocrine activities described here point to its role as an important regulator in communication between the immune and neuroendocrine systems.
 ...
PMID:IL-10 as a mediator in the HPA axis and brain. 1069 24

The production and secretion of peptides by adrenocortical tumors have not been well studied. We therefore studied the production and secretion of two vasoactive peptides, adrenomedullin and endothelin-1 in SW-13 human adrenocortical carcinoma cells by radioimmunoassay and Northern blot analysis. Both immunoreactive-adrenomedullin and immunoreactive-endothelin were detected in the culture medium of SW-13 cells (27.7 +/- 1.6 fmol/10 (5) cells/24 h and 11.0 +/- 0.8 fmol/10 (5) cells/24 h, respectively, mean +/- SEM, n = 6). Northern blot analysis showed the expression of adrenomedullin mRNA and endothelin-1 mRNA in SW-13 cells. On the other hand, no significant amount of calcitonin gene-related peptide, corticotropin-releasing hormone, neuropeptide Y, or urocortin was secreted by SW-13 cells. Treatment with ACTH (10(-9)-10(-7) mol/l), angiotensin II (10(-9)-10(-7) mol/l), or dexamethasone (10(-8)-10(-6) mol/l) for 24 h had no significant effects on immunoreactive-adrenomedullin levels and immunoreactive-endothelin levels in the culture medium of SW-13. Treatment with tumor necrosis factor (TNF)-alpha (20 ng/ml) increased significantly both immunoreactive-adrenomedullin levels and immunoreactive-endothelin levels in the culture medium. Interferon-gamma (100 U/ml) increased the immunoreactive-endothelin levels, but not immunoreactive-adrenomedullin levels, whereas interleukin-1 (IL-1)beta (10 ng/ml) increased immunoreactive-adrenomedullin levels, but not immunoreactive-endothelin levels. These findings indicate that SW-13 human adrenocortical carcinoma cells produce and secrete two vasoactive peptides, adrenomedullin, and endothelin-1 and that the secretion of these two peptides is modulated differently by cytokines.
 ...
PMID:Production and secretion of two vasoactive peptides, adrenomedullin and endothelin-1, by cultured human adrenocortical carcinoma cells. 1076 53


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>