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)

We evaluated the presence of anterior pituitary hormones; follicle-stimulating hormone (FSH) and its beta-subunit (beta-FSH), luteinizing hormone (LH) and its beta-subunit (beta-LH), beta-subunit of thyroid-stimulating hormone (beta-TSH), adrenocorticotropic hormone (ACTH), growth hormone (GH), and prolactin (PRL); the placental hormone human chorionic gonadotropin (hCG); and somatostatin, in paraffin and frozen sections of the human thymus. Epithelial cells in the medulla were immunoreactive for most of these hormones, in varying density and intensity of labeling. The cells labeled varied from epithelial cells surrounding Hassall's corpuscles toward solitary cells or small epithelial aggregates in the medulla. FSH immunoreactivity did occur predominantly in epithelial cells of the cortex, in apparent contrast to the predominant medullary location of cells immunolabeled for beta-FSH. The epithelial nature of FSH-immunoreactive cells was confirmed by two-color immunohistochemistry with anti-keratin antibody. In addition to FSH, some epithelial cells in subcapsule and cortex were labeled by antibodies to beta-FSH, beta-LH, beta-TSH, ACTH, GH, and PRL. Some macrophage-like cells surrounded by a rosette of lymphocytes were immunoreactive for FSH and GH. Some interdigitating reticulum-like cells were labeled by anti-beta-LH. Immunolabeling of lymphocytes was found for hCG, especially lymphocytes in the medulla. Two-color immunohistochemistry with anti-CD3 revealed a strong CD3 expression on hCG-immunoreactive cells, whereas CD3-negative cells were hCG-negative. T cells immunolabeled for hCG were also found in peripheral lymphoid organs.
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PMID:The neural and neuro-endocrine component of the human thymus. II. Hormone immunoreactivity. 139

Existence of proopiomelanocortin (POMC) messenger RNA (mRNA) and related peptides in extrapituitary sites has been demonstrated in immune cells, although the particular type of immune cell has been the source of considerable debate. Specifically, double labeling studies have shown that POMC peptide expressing cells in the spleen represent a subpopulation of red pulp macrophages, while splenic lymphocyte areas are POMC negative. In addition, it has also been reported that peripheral blood leukocytes express the POMC gene. Using a sensitive solution hybridization technique with a POMC exon-1 RNA probe, we detected 70 +/- 20 fg and 65 +/- 5 fg POMC mRNA per microgram total RNA in whole spleen and lung, respectively, approximately 20,000-fold lower concentrations than found in the neurointermediate lobe of the pituitary. The presence of nuclease protected full length exon-1 bands, rather than the 5' truncated POMC RNAs seen in many nonpituitary tissues, indicates transcription initiation at the normal pituitary POMC promoter site in lung and spleen. In order to localize POMC gene expression in these tissues we employed an in situ hybridization method. There was an intense signal in a small population of large mononuclear cells scattered throughout the splenic red pulp and lung parenchyma. In the lung, these cells were concentrated in the periarteriolar zone in a manner suggestive of migration from the intravascular lumen. These cells had a histomorphology suggestive of monocyte-macrophages. POMC mRNA was undetectable in the splenic white pulp and bronchus-associated lymphoid tissue, indicating an absence of POMC gene expression in splenic and lung lymphocytes. Immunocytochemical studies suggested that POMC-positive cells made up a subpopulation of cells expressing the rat monocyte-macrophage markers ED1 and ED2. Similarly, the distribution of Jenner-Giemsa stained monocyte-macrophages appeared to overlap with POMC positive cells. Studies with anti-rat beta-endorphin antisera revealed scattered cells in the splenic red pulp and lung parenchyma, suggesting that the POMC mRNA is translated in these cells. In summary, POMC mRNA is expressed in a small population of monocyte-macrophage-like cells in lung and spleen but not in lymphocytes in these tissues.
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PMID:Proopiomelanocortin gene expression in a distinct population of rat spleen and lung leukocytes. 161 33

The oxidative burst of rainbow trout (Oncorhynchus mykiss) phagocytes was previously found to be differentially modulated by adrenocorticotropic hormone (ACTH) and the catecholamine receptor agonists phenylephrine and isoproterenol. From data obtained using both luminol-enhanced chemiluminescence (LECL) and ferricytochrome C (cyt C) reduction to measure oxidative burst kinetics, we postulated that the observed modulation was mediated by affects on enzymes responsible for the production and metabolism of superoxide anion. Using exogenous superoxide dismutase (SOD) and catalase as scavengers, nitroprusside to poison endogenous SOD, and an assay for hydrogen peroxide, we have tested our postulates by exploiting the differences with which various reactive oxygen intermediates influence LECL and cyt C reduction. The ability of ACTH to potentiate both assays of the oxidative burst appears due to its enhancing influence on the production of superoxide. Phenylephrine, an alpha-adrenergic receptor agonist, appears to enhance the activity of endogenous SOD, whereas isoproterenol, a beta-adrenergic receptor agonist, may suppress SOD activity. This work reveals how components of the natural immune system may be regulated by products of the neuroendocrine system. Also, lymphocyte-derived ACTH may provide a novel pathway for lymphoid regulation of inflammation.
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PMID:Modulation of the oxidative burst in trout myeloid cells by adrenocorticotropic hormone and catecholamines: mechanisms of action. 165 72

Evidence has accumulated that human peripheral blood mononuclear cells (PBMC) may release adrenocorticotropic hormone (ACTH) and endorphin-like peptides into the culture medium when stimulated with different substances such as Newcastle disease virus and the lipopolysaccharide of Escherichia coli. However, to our knowledge, no quantitative assessment of ACTH-LIR (like-immunoreactivity) in human PBMC has been reported. We thus utilized a radioimmunoassay for ACTH to find a median of 30 pg of ACTH-LIR in 10(7) PBMC of 11 normal subjects. ACTH-LIR was also detected in 7 different cell lines derived from patients with lymphoid and myeloid malignancies, two of them, JM and U937, showed values of 135 and 108 pg/10(7) cells respectively. Stimulation with IL-1 beta at the concentration of 1000 U/mL induced, after 48 h, a significant increase of intralymphocytic ACTH levels when compared to basal and 24 h values. The chromatographic characterization of this ACTH-LIR showed, at least, three molecular forms of immunoreactive ACTH; molecular weights were 31 kD POMC, 22 kD ACTH and 4.5 kD ACTH. We used northern blotting with human genomic DNA probe for POMC gene to evidence specific mRNA in PBMC; mRNA was also observed in a T lymphocyte cell line derived from a patient with lymphoma. We conclude that PBMC produce ACTH-LIR which may act as a paracrine immunomodulator similar to lymphokine and/or may signal the adrenal gland to secrete glucocorticoids.
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PMID:[ACTH of lymphocytic origin under normal and pathological conditions]. 166 15

We have studied the effects of natural opioids on interleukin-1 (IL-1) -induced interleukin 2 (IL-2) production by the lymphoid cell line EL-4. beta-Endorphin (beta-end) significantly enhanced IL-2 production by IL-1-stimulated EL-4 cells. Similar results were obtained using the LBRM33-1A5 cell line. beta-End induced significant enhancement (35-100%) of IL-1-induced IL-2 production at all concentrations of IL-1 tested (2-0.25 U/ml) and the effects were seen with both IL-1 alpha and IL-1 beta. The dose response of beta-end augmentation of IL-1-induced IL-2 production was bimodal, with peak activities seen at high (10(-8)-10(-10) M) and low (10(-16) M) beta-end concentrations. The specificity of beta-end effect was studied using the opioid antagonist naloxone. Naloxone completely abolished the enhancing effects of beta-end, indicating that the effects might be mediated through binding to opioid receptors. In addition, other opioid peptides, including gamma-endorphin and enkephalins, elicited similar effects. Northern blotting analysis revealed higher levels of IL-2 mRNA in beta-end-treated IL-1-induced EL-4 cells than in IL-1-induced control cells. Thus, beta-end might enhance IL-2 production by either augmenting the transcription rate or increasing IL-2 mRNA stability. These results suggest that beta-end might play an important role in the regulation of lymphokine production in the periphery in addition to its known interactions with IL-1 in the central nervous system.
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PMID:Beta-endorphin modulation of IL-1-induced IL-2 production. 168 7

Because the immune response appears important in the pathogenesis of MS, anti-inflammatory and immunomodulatory drugs and agents are used as a palliative treatment. Azathioprine alone is minimally efficacious and probably not worth the bother and risk. Cyclophosphamide alone is too toxic. Although cyclosporine A may slow the rate of deterioration in chronic progressive MS, adverse effects may limit its use outside major centers. Gamma interferon provokes exacerbations and should not be used. We do not recommend copolymer-1, alpha or beta interferon, monoclonal antibodies, plasmapheresis, and total lymphoid irradiation except in well-designed experimental protocols. Combination therapy of adrenal cortical steroids (ACS) with other immunosuppressants (cyclophosphamide or cyclosporine) merits further study. We think "pulse" synthetic ACS therapy has advantages over corticotropin and will become the "standard of care" for exacerbations. We also would try it for chronic progression. Even then, with the pulse treatment we still must determine the optimum dose, route, duration, and need for "taper."
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PMID:The peculiar difficulties of therapeutic trials for multiple sclerosis. 169 Aug 38

The common acute lymphoblastic leukemia antigen (CALLA, CD10), which is expressed on early lymphoid progenitors and neutrophils, is the zinc metalloprotease, neutral endopeptidase 24.11 (NEP, "enkephalinase"). The CD10 cell surface enzyme is known to hydrolyze a variety of biologically active peptides including met-enkephalin, formyl-met-leu-phe (f-MLP), and substance P. These three CD10/NEP substrates induce the migration and aggregation of neutrophils, suggesting that each of the peptides can function as a mediator of neutrophil inflammatory responses. Recently, inhibition of CD10/NEP was found to reduce the concentration of metenkephalin needed to activate human and invertebrate granulocytes by several orders of magnitude. Herein we show that f-MLP and substance P induce rapid changes in neutrophil morphology, migration, and adhesion molecule expression, including upregulation of Mo1 (CD11b/CD18) and shedding of LAM-1 (also known as LECAM-1, Leu8, or TQ-1, the human homologue of murine gp100MEL14). Importantly, these coordinated changes are potentiated by inhibition of cell surface CD10/NEP enzymatic activity. Neutrophil cell surface CD10/NEP enzymatic activity is also shown to be regulated by the activation state of the cell during the time period in which the enzyme has its most pronounced effects. These results suggest that in neutrophils, CD10/NEP functions to control responsiveness to multiple inflammatory peptides.
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PMID:CD10 (CALLA)/neutral endopeptidase 24.11 modulates inflammatory peptide-induced changes in neutrophil morphology, migration, and adhesion proteins and is itself regulated by neutrophil activation. 171 72

Human peripheral blood mononuclear cells are analyzed for preproenkephalin gene expression and peptide processing. Met-enkephalin immunoreactivity as detected with a specific antiserum is found in the cytoplasm of monocytes but not in T lymphocytes. Secretion of met-enkephalin was analyzed with an RIA that is specific for the met-enkephalin pentapeptide. Unfractionated PBMC spontaneously released 40 pg/ml met-enkephalin and this increased two- to fourfold after stimulation with PHA. Lower levels (less than 100 pg/ml) of met-enkephalin were detected in supernatants from purified T cells that were activated with PHA and IL-2. In contrast, stimulation of purified monocytes with LPS or PMA resulted in the release of up to 600 pg/ml of the processed peptide. To examine whether T cells can produce met-enkephalin precursor peptides, T cell conditioned media were treated with trypsin and carboxypeptidase-B, which is known to release met-enkephalin from the propeptide. This increased levels of met-enkephalin to 400 pg/ml, indicating that lymphocytes secrete the propeptide but do not process it to met-enkephalin. The 1.4-kb preproenkephalin mRNA is detected in activated blood mononuclear cells and in purified monocytes and T cells. To determine whether monocytes or lymphocytes express met-enkephalin in vivo, lymphoid tissues were analyzed by immunohistochemistry. In human spleen tissue, positive cells were found in the red pulp but not in the follicles, which is also consistent with met-enkephalin expression in monocytes. In summary, these results show that human peripheral blood mononuclear cells express preproenkephalin mRNA and that monocytes, but not T cells, process the propeptide to metenkephalin.
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PMID:Differential processing of proenkephalin-A by human peripheral blood monocytes and T lymphocytes. 188 71

In the hematopoietic system a pluripotent stem cell generates precursors for lymphoid and myeloid lineages. Proenkephalin-derived peptides were previously detected in differentiated lymphoid cells. We have studied whether the proenkephalin system is expressed in a typical differentiated cell of the myeloid lineage, the neutrophil. Human peripheral polymorphonuclear cells contain and release proenkephalin-derived peptides. The opioid portion of proenkephalin (met-enkephalin-containing peptides) was incompletely processed, resulting in the absence of low molecular weight products. The nonopioid synenkephalin (proenkephalin 1-70) molecule was completely processed to a 1.0-kD peptide derived from the COOH-terminal. This molecule was characterized in neutrophils by biochemical and immunocytochemical methods. The chemotactic peptide FMLP and the calcium ionophore A23187 induced the release of the proenkephalin-derived peptides, and this effect was potentiated by cytochalasin B. The materials secreted were similar to those present in the cell, although in the supernatant a higher proportion corresponded to more processed products. The 1.0-kD peptide was detected in human, bovine, and rat neutrophils, but the chromatographic pattern of synenkephalin-derived peptides suggests a differential posttranslational processing among species. These findings demonstrate the existence of the proenkephalin system in human neutrophils and the production and release of a novel 1.0-kD peptide derived from the synenkephalin molecule. The presence of opioid peptides in neutrophils suggests their participation in the inflammatory process, including a local analgesic effect.
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PMID:Proenkephalin system in human polymorphonuclear cells. Production and release of a novel 1.0-kD peptide derived from synenkephalin. 211 23

Cocaine acts directly on lymphoid cells and indirectly modulates the immune response by affecting the level of neuroendocrine hormones. In vitro, very high concentrations of cocaine inhibit different immune responses, while plasma levels following cocaine use have no effect. The results of the few published in vivo studies are contradictory, showing stimulatory, suppressive or no effect on lymphoid cells. The indirect effects of cocaine on the immune system could be mediated by ACTH, beta-endorphin and corticosterone. Anorectic effect associated with nutritional deficiencies of drug users could additionally affect the immune response by cocaine.
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PMID:Immunomodulation by cocaine--a neuroendocrine mediated response. 218 49


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