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

The neuropeptide alpha-melanocyte stimulating hormone [alpha-MSH(1-13)] occurs in the pituitary, brain, skin and other tissues and receptors for this molecule are likewise widespread. In previous research, this tridecapeptide, which shares its amino acid sequence with ACTH(1-13), was shown to have both potent antipyretic activity and a role in the endogenous control of the febrile response. alpha-MSH(1-13) and its COOH-terminal tripeptide were subsequently found to inhibit inflammation induced by general stimuli such as topical application of an irritant. The aim in the present experiments was to determine if these peptides can inhibit acute inflammatory responses induced in mice by injection of individual cytokines, endogenous pyrogen (EP), a natural cytokine mixture, and other mediators of inflammation. Inflammation induced in the mouse ear by rIL-1 beta, rIL-6 or rTNF-alpha was inhibited by alpha-MSH and a D-valine-substituted analog of alpha-MSH(11-13) whereas substantial doses of alpha-MSH(1-13) did not alter inflammation induced by LTB4, PAF and IL-8. Both peptides inhibited edema caused in the mouse paw by local injection of EP. The results indicate that alpha-MSH molecules antagonize the actions of certain cytokine mediators of inflammation, consistent with previous observations of anti-cytokine activity of these peptides. Failure to inhibit edema caused by LTB4, PAF and IL-8 suggests that, in inflammation induced by general stimuli, such as EP, the peptides act prior to the release of these mediators of the inflammatory response. Because of the anticytokine/anti-inflammatory actions of the alpha-MSH molecules they may be useful in understanding the cytokine network and for treatment of inflammatory diseases.
Cytokine 1992 Jul
PMID:Alpha-MSH peptides inhibit acute inflammation induced in mice by rIL-1 beta, rIL-6, rTNF-alpha and endogenous pyrogen but not that caused by LTB4, PAF and rIL-8. 132 96

A lipopolysaccharide from Pantoea agglomerans (LPSp) was purified and examined for relief of morphine dependence by observing its inhibition of the jumping of mice on naloxone-precipitate withdrawal. Administration of LPSp either intravenously or intradermally showed marked inhibition of the jumping. Beta-endorphin in mouse serum and brain tissue were recognized to be in synchrony with the time course of the relief. Administration of TNF-alpha gave similar effect, suggesting that LPSp induces a cytokine cascade to produce endogenous TNF followed by ACTH/beta-LPH gene products and beta-endorphin. The effect of LPSp was better than that of LPS from E. coli or Bordetella pertussis, and thus is considered to be applicable for clinical use.
Eur Cytokine Netw
PMID:Inhibition of morphine dependence by a lipopolysaccharide from Pantoea agglomerans. 142 Oct 14

beta-endorphin, when added at the same time as the mitogenic lectin concanavalin A to mouse BALB/c spleen lymphocytes, inhibits cell proliferation. The suppressive effect of beta-endorphin is not exercised through a cAMP-dependent mechanism and is also observed when splenic lymphocytes are stimulated with phytohemagglutinin (4 micrograms/ml), anti-CD3 monoclonal antibody, or the Ca2+ ionophore A23187 (250 nM) and phorbol 12-myristate 13-acetate (1 ng/ml). The inhibitory effect of beta-endorphin on lymphocyte proliferation is dose and time dependent: when beta-endorphin is added 20 h after Con A stimulation no suppression of lymphocyte proliferation is observed. beta-Endorphin inhibits, in a dose-dependent manner, the release of interleukin-2 in concanavalin A-stimulated splenic lymphocytes, measured 24 h after stimulation. beta-Endorphin also controls the appearance of interleukin-2 receptors in the plasma membrane, but does not regulate the expression of the c-myc protooncogene. These data indicate that beta-endorphin inhibits lymphocyte activation signal transmission, downstream the generation of the second messengers Ca2+ and diacylglycerol and the expression of the protooncogene c-myc, by blocking interleukin-2 release and interleukin-2 receptors expression. Once the cells are in the G1 stage, beta-endorphin is no longer able to block lymphocyte proliferation.
Lymphokine Cytokine Res 1992 Dec
PMID:Beta-endorphin inhibits interleukin-2 release and expression of interleukin-2 receptors in concanavalin A-stimulated splenic lymphocytes. 147 86

Interleukin-1 (IL-1) and interleukin-6 (IL-6) share a number of biological functions. Because IL-1 induces IL-6 in vivo, the extent to which IL-6 mediates the effects of IL-1 has come under investigation. The stimulation of the hypothalamic-pituitary-adrenal axis by IL-1 and IL-6 is a critical component of the inflammatory response. The present study was designed to compare the effects of recombinant human IL-1 alpha (rhIL-1 alpha) and recombinant human IL-6 (rhIL-6) administered in combination and alone on the release of adrenocorticotropic hormone (ACTH) in mice. We have demonstrated that the administration of rhIL-6 alone does not duplicate the stimulatory effect of rhIL-1 alpha on ACTH release. On the other hand, suboptimal amounts of rhIL-1 alpha and rhIL-6 synergize to induce an early (30-60 min) ACTH response and produce a later (2-3 h) response that is similar to the one observed after rhIL-1 alpha is administered alone. These results suggest that the 2-3 h response to rhIL-1 alpha may be dependent on synergy with the endogenous IL-6 it induces systemically and in the central nervous system (including the hypothalamus and the pituitary gland).
Lymphokine Cytokine Res 1991 Apr
PMID:Interleukin-1 and interleukin-6 act synergistically to stimulate the release of adrenocorticotropic hormone in vivo. 165 67

Cytokine-mediated communication between the immune system and the nervous system has been shown in the past few years. The precise cellular sources of these molecules in the brain is still a controversial issue. We have thus immortalized primary cell cultures from mouse embryonic brains to analyze cloned cells involved in cytokine production. The cell clones obtained were identified as microglial cells and shown to produce several monokines. Among these, TNF alpha was detected by molecular analysis and cytotoxicity assays and shown to be expressed by microglial cells, after activation with LPS. Surprisingly, the TNF alpha-mediated cytotoxic activity, which was neutralized by specific antisera, was not detected in the cell supernatants but was mediated through cell-to-cell contact. Using antibodies to TNF alpha in FACS analysis, specific cell membrane staining on live microglial cells was shown. The results suggest that in the brain the form of TNF alpha detectable by standard procedures is the cell bound form and not the most common form, secreted TNF alpha. In addition, the effects of recombinant TNF alpha in vitro and in vivo were evaluated. In vitro, rTNF alpha stimulated beta-endorphin, GH, and PRL release from cultured cells prepared from rat anterior pituitary glands. In vivo, the administration of rTNF alpha to rats was able to modify analgesic responses. The concomitant administration of naloxone, an opiate receptor antagonist, or monoclonal anti-IL-1 antibody decreased the analgesic effects induced by rTNF alpha. This indicates that the analgesic effect might not be mediated directly by rTNF alpha but by other mediators, whose action is under the control of TNF alpha.
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PMID:Cellular sources and effects of tumor necrosis factor-alpha on pituitary cells and in the central nervous system. 237 85

Cytokine-induced release of corticotropin-releasing factor (CRF) from hypothalamic explants in vitro can be inhibited by femtomolar concentrations of alpha-melanocyte-stimulating hormone (alpha-MSH). Because the mechanism of the anticytokine action of alpha-MSH remains unknown, we examined if the peptide inhibits CRF release by interference with various steps in the activation of CRF release. Previous studies have shown that CRF release is induced by activation of phospholipase A2 (PLA2). Therefore, we examined the effect of alpha-MSH on the action of melittin (MEL), a PLA2 activator. After 60 min preincubation in Krebs-Ringer bicarbonate buffer, medial basal hypothalami were incubated for 30 min with Krebs-Ringer bicarbonate buffer or MEL with or without alpha-MSH (10(-11) to 10(-16) M). CRF release into the incubation medium was measured by RIA. As reported previously none of the alpha-MSH concentrations used changed basal CRF release nor did any concentration of alpha-MSH significantly alter CRF release induced by MEL (10 micrograms/ml). Thus, alpha-MSH alters cytokine-induced CRF release at a step unrelated to the activation of PLA2. Because activation of PLA2 requires an increase in intracellular calcium ion (Ca2+) concentrations, we evaluated the effect of alpha-MSH on the release of CRF induced by a high concentration of potassium (56 mM). This concentration of potassium induced a 3.5-fold increase in CRF release that was not affected by alpha-MSH. Protein kinase C (PKC) stimulates CRF release. Consequently, we examined the effect of alpha-MSH on CRF release induced by phorbol myristate acetate (PMA), which in the presence of Ca2+ stimulates PKC.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Alpha-melanocyte-stimulating hormone inhibits corticotropin-releasing factor release by blocking protein kinase C. 748 28

We recently demonstrated that the opioid peptide beta-endorphin (beta-End) has the capacity to stimulate interleukin-2 (IL-2) and IL-4 production by murine CD4+ T cells. Since opioid peptides have been demonstrated to contain stimulatory as well as inhibitory sites, we studied peptide fragments of beta-End to identify a moiety with exclusive stimulatory capacity. To this end, the effects of various opioid peptides on the production of IL-2, IL-4, IL-6, and interferon-gamma (IFN-gamma) by CD4+ T cells were determined. It appeared that two peptide fragments of beta-End, i.e., beta-End6-31 and beta-End18-31, that lack the N-terminal enkephalin part, enhanced IL-2 and IL-4 production to a similar extent as intact beta-End, indicating that the N-terminal part is not involved in the stimulating effects of beta-End. Also the production of IL-6 and IFN-gamma was increased by these peptides. By contrast, the fragments beta-End24-31 and beta-End28-31 did not stimulate the production of the cytokines. Surprisingly, also alpha-End, which is equivalent to beta-End1-16 and hence lacks the sequence comprising amino acids 18 through 31, was stimulatory. This effect was not prevented by naloxone, indicating that opioid receptors were not involved. Moreover, methionine-enkephalin (Met-Enk), which binds to opioid receptors, did not affect cytokine production. Because both alpha-End and beta-End18-31 stimulate cytokine production by CD4+ T cells and do not overlap is sequence, it is concluded that at least two distinct sites of beta-End can exert stimulating effects on cytokine production.
Lymphokine Cytokine Res 1994 Apr
PMID:Identification of distinct sites of beta-endorphin that stimulate lymphokine production by murine CD4+ T cells. 791 52

We have investigated whether parotin subunit (PS) and its partial synthetic peptide (P-10.2: TDDTAIVLLK), possess interleukin 1 (IL-1)-like activities, and act on cell lines other than lymphocytes. When Chang liver cells were cultured with P-10.2, PS or IL-1, P-10.2 and PS augmented the growth of Chang liver cells. On the other hand, IL-1 enhanced the growth of Change liver cells at 1 day of the initial culture and subsequently failed to enhance during at least 4-day incubation. Next, effects of P-10.2 and PS on the growth of Alexander cells and MH134 were investigated. The proliferation of Alexander cells was inhibited with P-10.2 or PS but not with IL-1. P-10.2 inhibited the growth of MH134 at day 1 and 3, while the growth of MH134 was shown not to be inhibited with PS and IL-1 at day 1, but rather suppressed them at day 3. These results suggest that P-10.2 augments the growth of non-malignant liver cells (Chang liver cells) but inhibits that of hepatoma cells (Alexander cells and MH134). P-10.2 enhanced fibrinogen and hepatoglobin secretion from Chang liver cells. In addition to their liver cell activation, P-10.2 and PS stimulated ACTH and beta-endorphin secretion from AtT-20 cells.
Cytokine 1994 May
PMID:Parotin subunit and its synthetic peptide possess interleukin 1-like activity and exert stimulating effects on liver cells and brain cells. 805 82

It is well known that interleukin (IL)-1 is a potent activator of the hypothalamo-pituitary-adrenal axis in the rat. Many studies have reported that prostaglandins (PGs), especially PGE2, in the brain may mediate the IL-1 stimulation of corticotropin-releasing hormone release, which then leads to adrenocorticotropin (ACTH) secretion. However, a general consensus has yet to emerge regarding whether PGE2 is the only or the most important PG in the brain mediating IL-1-induced ACTH secretion in the rat. To address this question, we examined the effect of intracerebroventricular (icv) administration of antisera against PGE1, PGE2 or PGF2 alpha, or normal rabbit serum on the ACTH response induced by an icv injection of IL-1 beta in the rat. Each antibody or normal rabbit serum (as the control) was given icv 15 min before an icv administration of human recombinant IL-1 beta (50 ng). IL-1 beta produced a significant rise in plasma ACTH levels, and this response was significantly suppressed by either of the three PG antibodies. Interestingly, the inhibitory effect of anti-PGE2 antibody seemed to be somewhat weaker than those of the other two antibodies. We conclude that not only PGE2 but also PGE1 and PGF2 alpha in the brain may mediate the IL-1 beta stimulation of ACTH secretion in the rat.
Cytokine 1995 Oct
PMID:Role of prostaglandins E1, E2 and F2 alpha in the brain in interleukin 1 beta-induced adrenocorticotropin secretion in the rat. 858 Mar 80

We investigated the effects of recombinant human IL-1 alpha, -1 beta, -2, -6 and TNF on the in vitro secretion of beta-endorphin-immunoreactivity (beta E-IR) by the rat anterior and neurointermediate lobes (AL and NIL, respectively) and of B by the rat adrenal gland. Isolated AL and NIL cells were incubated for 2 h with cytokines (1 pg/m1(-1) mu g/ml), CRH (5.10(-10) M) or with cytokines in combination with CRH (AL cells), isolated adrenal cells were incubated for 2 h with cytokines, ACTH (25 pg/ml) or with cytokines in combination with ACTH. Furthermore, AL, NIL and adrenal tissue fragments were superfused for 30 or 60 min with cytokines (10 and/or 100 ng/ml). Incubation of AL, NIL and adrenal cells and superfusion of these tissues with cytokines had no significant effect on beta E-IR and B release. However, there are some exceptions: incubation of AL cells with IL-2 increased CRH-induced beta E-IR release, incubation of NIL cells with IL-2 induced an increase of basal beta E-IR release, ACTH-induced B secretion was reduced after co-incubation of adrenal cells with TNF and after prolonged (6 h) superfusion of adrenal tissue with TNF, and finally, prolonged (6 h) superfusion of adrenal fragments with IL-1 beta increased basal B release. Taken together, these data suggest that the acute activation of the pituitary-adrenal axis of rats by administration of cytokines (at least IL-1, IL-6 and TNF) in vivo is not mediated by a direct action of these cytokines at the level of the pituitary and/or adrenal gland.
Cytokine 1996 Mar
PMID:Effects of cytokines on pituitary beta-endorphin and adrenal corticosterone release in vitro. 883 39


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