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)

Previous reports have shown that there is an endogenous opioid component associated with pathophysiological responses to endotoxin. It has been shown that these responses are alleviated by naloxone, a specific opiate antagonist. Results of another study have indicated that leukocytes may mediate some of those responses since leukocyte depletion alleviated the effects of lipopolysaccharide. In view of the above reports as well as the finding that leukocytes produce immunoreactive (ir-) endorphins and corticotropin (ACTH) when stimulated with Newcastle disease virus or ACTH-releasing factor, we postulated that leukocytes may serve as an extrapituitary source of endorphins produced in response to bacterial endotoxin. To test this hypothesis, human peripheral blood leukocytes as well as mouse spleen cells were cultured in vitro with Escherichia coli lipopolysaccharide for 48 h. The lipopolysaccharide (i.e., endotoxin) was shown to induce de novo synthesis of ir-ACTH and ir-endorphins. The leukocyte-derived ir-ACTH had a molecular weight of approximately 2,900 and demonstrated a bioactivity similar to that of pituitary-derived ACTH. The lymphocyte-derived ir-endorphin comigrated with alpha- and gamma-endorphin at approximately 1,800 daltons and was shown to bind to brain opiate receptors. These findings imply that leukocyte-derived endorphins may be involved in the pathophysiological response to endotoxin.
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PMID:Bacterial lipopolysaccharide induction of leukocyte-derived corticotropin and endorphins. 298 31

The opioid peptides alpha- and beta-endorphin and [D-Ala2, Met5]enkephalin were investigated for their effect on the proliferation of resting and activated rat splenic lymphocytes in vitro. beta-Endorphin enhanced the proliferative response of spleen cells to the T cell mitogens concanavalin A and phytohemagglutinin. The effect of beta-endorphin was dose dependent and occurred at peptide concentrations similar to those found in rat plasma. alpha-Endorphin and [D-Ala2, Met5]enkephalin did not affect the proliferative responses to any mitogen tested. Furthermore, the potentiating effect of beta-endorphin was not reversed by treatment with 10 microM naloxone. None of the peptides had any effect on resting, unstimulated spleen cells or on the response to a mixture of lipopolysaccharide and dextran sulfate, which is specifically mitogenic for B lymphocytes. The pharmacological properties of the beta-endorphin potentiation indicate that the effect may be mediated by a nonopiate but beta-endorphin-specific mechanism. These results suggest a possible role for peripheral beta-endorphin and may provide a link between stress and disease susceptibility.
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PMID:beta-Endorphin enhances lymphocyte proliferative responses. 628 75

To study whether hemorrhage stimulates interleukin-6 (IL-6) production in conscious rats, 30% of the total blood was withdrawn over 3 min through an indwelling venous catheter and the shedblood was reinfused 1 h later. Plasma adrenocorticotropic hormone (ACTH), corticosterone and IL-6 concentration rapidly increased. Plasma ACTH levels peaked at 10 min and corticosterone and IL-6 peaked at 60 min; all started to decrease after reinfusion. In adrenalectomized (ADX) rats with or without a corticosterone pellet implant, there was an inverse relationship between IL-6 and corticosterone concentrations, greatest in ADX rats and lowest in ADX rats in which plasma corticosterone was elevated by crushing the implanted pellet. However, the ADX rats in which plasma corticosterone was maintained at normal or slightly elevated levels showed greater IL-6 responses to hemorrhage and elevated basal plasma IL-6 levels compared to sham-operated control rats. Twenty-four hours after hemorrhage/reinfusion, ACTH, corticosterone, and IL-6 responses to i.v. injection of lipopolysaccharide (LPS) were all reduced compared to the non-hemorrhaged animals, indicating that hemorrhage impaired general host defense. Although very high plasma corticosterone concentrations markedly suppressed the IL-6 response to LPS, in ADX rats in which plasma corticosterone was maintained at slightly higher levels than normal, the reduced IL-6 response to LPS in the posthemorrhage period was not reversed, but enhanced. Thus corticosterone has biphasic effects on the IL-6 response to hemorrhage and the response to LPS during the posthemorrhage period, which has important clinical implications with regard to the optimal dose of glucocorticoid for maintaining the host defense response.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Rapid increase in plasma IL-6 after hemorrhage, and posthemorrhage reduction of the IL-6 response to LPS, in conscious rats: interrelation with plasma corticosterone levels. 748 23

The present study was performed to investigate the effect of beta-endorphin on macrophage colony-stimulating factor (M-CSF)-induced differentiation of macrophages from bone marrow cells in a semisolid culture system. beta-endorphin increased the number of macrophage colonies when bone marrow cells were cultured in the presence of M-CSF plus lipopolysaccharide (LPS). This was not the case with LPS-unresponsive C3H/HeJ mouse bone marrow cells. alpha-endorphin and gamma-endorphin were as effective as beta-endorphin in enhancing the colony formation. Exogenous interleukin-1 (IL-1), but neither IL-6 nor tumor necrosis factor (TNF), collaborated with beta-endorphin even in the absence of LPS, suggesting that IL-1 is a primary mediator of the effect of LPS. Indeed, anti-IL-1 antibody abolished the collaborative effect of beta-endorphin with LPS. Moreover, IL-1 was effective even for C3H/HeJ mouse bone marrow cells. Naloxone, an antagonist of endorphins for opioid-receptors, completely abrogated the effect of beta-endorphin. In a single-cell culture system, the collaboration between beta-endorphin and IL-1 was revealed by the increase in number and size of macrophage colonies, but collaboration between beta-endorphin and LPS did not occur. These results indicate that, in mixed cell culture, beta-endorphin acts in concert with paracrinal IL-1 induced by LPS to enhance M-CSF-dependent macrophage differentiation from immature precursor cells.
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PMID:Enhancement of murine bone marrow macrophage differentiation by beta-endorphin. 754 4

There is increasing evidence indicating that the production of cytokines and prostaglandins (PG) may be interrelated and is regulated by glucocorticoids (GC). In the present study we examined the effect of the bacterial endotoxin lipopolysaccharide (LPS) and interleukin-1 (IL-1) on the ex vivo production of PGE2 by the dorsal hippocampus of the mouse which contains high levels of receptors to IL-1. The roles of IL-1 receptors and GC in the regulation of LPS- or IL-1-induced PGE2 production were also studied. In control mice the basal rate of PGE2 ex vivo synthesis by slices of dorsal hippocampus was about 250 pg/mg protein/60 min. Intraperitoneal injection of either LPS (1-50 micrograms/mouse) or IL-1 alpha (50-200 ng/mouse) increased the production of PGE2 in a dose-and time-dependent manner. Both LPS and IL-1 alpha induced a maximal 2.5-fold increase in PGE2 production at 6 h after the injections. IL-1 beta was less effective by approximately 30% as compared to IL-1 alpha. In mice treated with the IL-1 receptor antagonist or with the IL-1 antagonist alpha-melanocyte-stimulating hormone (alpha-MSH), the effects of LPS and IL-1 on PGE2 production were completely abolished. Intraperitoneal injections of dexamethasone (DEX) 5 or 30 micrograms/mouse 2 h prior to the administration of IL-1 alpha significantly enhanced the effect of the cytokine on PGE2 production. In mice treated with 100 micrograms DEX/mouse, the facilitatory effect of the lower DEX does in IL-1-induced PGE2 production was abolished.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of bacterial endotoxin and interleukin-1 on prostaglandin biosynthesis by the hippocampus of mouse brain: role of interleukin-1 receptors and glucocorticoids. 756 37

The effect of an i.p. bolus injection of 200 micrograms.kg-1 bacterial lipopolysaccharide (LPS) on the plasma concentrations of ACTH and corticosterone (B) were studied in intact and hypophysectomized/ACTH replaced (Hx) rats. Hormonal blood levels were measured by RIA, 30, 60, 120, 180 and 240 min after the injection. The stress evoked by the vehicle i.p. injection provoked significant rises in ACTH and B blood levels at 30 and 60 min in intact rats, but not in Hx animals. In intact rats, LPS enhanced (over the respective control value) ACTH plasma level at 60, 120 and 180 min, and B plasma concentration at 120, 180 and 240 min. In Hx rats, LPS did not affect ACTH blood level, but raised B plasma concentration at 60, 120 and 180 min. B response to LPS at 120 min was completely annulled, in both intact and Hx rats, by the simultaneous administration of 25 nmol.kg-1 alpha-helical-CRH and corticotropin-inhibiting peptide that are competitive inhibitors of CRH and ACTH, respectively. The hypothesis is advanced that LPS may activate hypothalamo-pituitary adrenal axis in rats, by stimulating not only the central (hypothalamo-pituitary), but also the peripheral (intra-adrenal) branch of the CRH/ACTH system.
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PMID:Bacterial lipopolysaccharide stimulates glucocorticoid secretion in hypophysectomized rats. 758 23

Increased arterial blood pressure following a pyrogenic reaction has been reported in previous studies, however the mechanism of this hypertension has not been examined in detail. The present study investigated the effects of both intravenous (IV) and intracerebroventricular (ICV) injection of lipopolysaccharide (LPS) from E. coli on body temperature (Tb), mean arterial pressure (MAP), heart rate (HR), cardiac output (CO), calculated total peripheral resistance (CTPR), stroke volume (SV) and plasma levels of adrenocorticotropin (ACTH) and arginine vasopressin (AVP) in conscious, chronically instrumented sheep. IV injection of LPS (1 microgram) increased Tb in a biphasic manner from 38.7 +/- 0.1 to 39.5 +/- 0.2 degrees C after 50 min and to 39.9 +/- 0.2 degrees C after 130 min, and MAP increased biphasically from 64 +/- 1 to 70 +/- 4 mmHg after 40 min and to 78 +/- 3 mmHg after 130 min. CO initially decreased from 4.4 +/- 0.1 to 3.5 +/- 0.1 after 40 min followed by a secondary rise to 4.8 +/- 0.1 l/min after 100 min. This occurred together with a large, biphasic increase in CTPR from 14.5 +/- 1.0 to 22.0 +/- 2.0 mmHg/l/min at 40 min, and to 18.1 +/- 0.1 mmHg/l/min at 120 min. HR increased from 68 +/- 4 to 97 +/- 4 b/min and SV decreased from 65 +/- 2 to 41 +/- 4 ml/beat during the first phase of activation. Plasma ACTH increased from 22 +/- 9 to 1043 +/- 175 pg/ml after 80 min, and plasma AVP increased from 0.7 +/- 0.2 to 12 +/- 4.0 pg/ml after 60 min. ICV injection of LPS produced a long-lasting increase in Tb and MAP, but had no effect on HR or plasma AVP. Plasma ACTH increased from 30 +/- 12 to 427 +/- 110 pg/ml. These changes suggest that intravenous pyrogenic infection produces a potent vasoconstrictor action in sheep to increase blood pressure, possibly mediated by the actions of AVP within the CNS, or other pyrogenically released vasoconstrictor factors. Furthermore, the duration of activation of the cardiovascular system following peripheral and central LPS administration is different, which together with the contrasting effects on ACTH and AVP, indicate the involvement of several hypertensive mechanisms.
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PMID:Pyrogenic stimulation of vascular resistance in conscious sheep. 762 27

The immediate-early gene NGFI-B encodes an orphan nuclear receptor that binds DNA as a monomer and activates transcription through a canonical response element (NBRE). NGFI-B is expressed under basal conditions and in response to external stimuli in many mammalian tissues. In particular, NGFI-B expression is dramatically elevated in the adrenal cortex in response to stress and in Y1 adrenocortical cells in response to adrenocorticotropin. NGFI-B activates transcription through an NBRE of the gene encoding 21-hydroxylase (P450c21) in Y1 cells. Steroidogenic factor 1 (SF-1), a homolog of NGFI-B, also activates the P450c21 promoter. To examine the influence of these factors on P450c21 expression in vivo and the function of the hypothalamic-pituitary-adrenocortical axis as a whole, we generated NGFI-B (-/-) mice. These mice thrive and reproduce normally and maintain normal basal adrenocorticotropin, corticosterone, and P450c21 mRNA levels. In response to increases in adrenocorticotropin, NGFI-B (-/-) and wild-type mice demonstrated equivalent increases in serum corticosterone levels. Furthermore, and in contrast to in vitro results, no increases in P450c21 mRNA levels were observed in response to increases in adrenocorticotropin in NGFI-B (-/-) or wild-type mice. While SF-1 mRNA levels were not increased with increased steroidogenic demand, adrenal expression of Nurr1, a close homolog of NGFI-B, was induced to a greater extent by lipopolysaccharide in NGFI-B (-/-) mice than in wild-type mice. Finally, when the administration of dexamethasone for suppression was stopped, P450c21 mRNA and serum corticosterone levels recovered at the same rate in wild-type and NGFI-B (-/-) mice. Thus, while NGFI-B appears poised to affect the structure and function of the adrenal gland, the gland functions normally in its absence, suggesting that other factors, including Nurr1 and SF-1, are sufficient to drive P450c21 expression in mice and maintain normal steroidogenesis.
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PMID:Adrenocortical function and regulation of the steroid 21-hydroxylase gene in NGFI-B-deficient mice. 762 27

Previously we have reported that in asthmatics an inhalation of 20 micrograms lipopolysaccharide (LPS) produces a bronchial obstruction associated with an inflammatory blood response. The aim of the present study was to evaluate this response in normal subjects. Eight normal non-atopic subjects were challenged by inhalation of a solution containing 20 micrograms LPS (from Escherichia coli 026:B6) a week after bronchial challenge with control solution. The lung function response was evaluated by the changes in forced expiratory volume in one second (FEV1), in specific conductance and in airway resistance while the blood inflammatory response was evaluated by serial measures of total white blood cells (WBC) and polymorphonuclear neutrophils (PMN) count, luminol enhanced-chemiluminescence (luminol-CL, as a marker of the PMN degree of activation), C-reactive protein (CRP), haptoglobin, complement fraction C3, tumour necrosis factor-alpha (TNF-alpha) and adrenocorticotropic hormone (ACTH). No response in lung function was observed for 6 h after the LPS inhalation. The count in WBC and PMN increased 300 (P < 0.01) and 360 (P < 0.01) min after the LPS challenge associated with an increase in the level of luminol-CL (P < 0.001). This rise in luminol-CL level was significant at 120 min (P < 0.05) before any change in the PMN count. After 24 and 48 h the acute-phase protein CRP raised significantly (P < 0.01), the other proteins C3 and haptoglobin being unchanged. A slight increase in ACTH was observed 240 and 360 min (P < 0.05) after the LPS challenge while the TNF alpha detectable level was not modified.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Blood inflammatory response to inhaled endotoxin in normal subjects. 772 26

The effects of long-term corticotropin-releasing hormone (CRH) infusion in the lateral ventricle of the rat on hypothalamic-pituitary-adrenocortical (HPA) axis parameters and on the immune system function were studied. Compared with infusion of vehicle, the CRH treatment produced a sustained overactivity of the HPA axis, as evidenced by elevated plasma ACTH and corticosterone levels, increased anterior pituitary POMC messenger RNA (mRNA) expression, and adrenal enlargement. Long-term CRH treatment also inhibited body weight gain and reduced thymus and spleen weight. In the CRH-treated animals, both Concanavalin A (Con A)-induced T lymphocyte proliferation and lipopolysaccharide (LPS)-induced B lymphocyte mitogenesis was largely suppressed. Surprisingly, interleukin-2 (IL-2) levels were higher in supernatants of splenocyte cultures from CRH-treated rats than in those of control animals. However, IL-2 receptor alpha chain (IL-2R alpha) mRNA expression after Con A stimulation was highly suppressed in the CRH-treated animals. In addition, Northern blot analysis of RNA from splenocytes isolated from spleens of CRH-treated rats revealed a marked expression of IL-1 beta mRNA, in contrast to the barely detectable levels of this cytokine in control animals. Moreover, incubation of total splenocytes and spleen macrophages with LPS resulted in an enhanced induction of IL-1 beta mRNA in cells of CRH-treated rats compared with that of control animals. When adrenalectomized rats were treated with CRH or vehicle, the effects of the CRH treatment on T and B cell proliferation, IL-2 production, and IL-1 beta mRNA expression were abolished. Thus, a continuously increased HPA axis drive results in disparate changes in immune system function. Whether the observed changes in cytokine expression should be regarded as physiologically adaptive adjustments in support of immune function or as potentially pathological anomalies remains to be elucidated.
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PMID:Long-term intracerebroventricular corticotropin-releasing hormone administration induces distinct changes in rat splenocyte activation and cytokine expression. 775 Apr 92


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