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 presence of adrenocorticotropic hormone (ACTH) and substance P (SP) receptors on leukocytes is suggestive that these cells can respond to these ligands. To address this possibility, we have investigated the consequences of ACTH and SP stimulation of B cells. As a result, enhanced immunoglobulin synthesis mimicking an IL-4-like mechanism was noted. Importantly, this stimulation could be induced at ligand concentrations at or near the kD for their receptors. Herein these effects by ACTH and SP were described using B cell lymphoma cell lines and normal B cells.
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PMID:The regulation of antibody responses by mini-cytokines. 172 64

In recent years there has been considerable discussion of possible cross-regulatory mechanisms involving the immune system and the neuroendocrine system. Certainly, evidence of hormonal communication between these two systems would provide at least a partial explanation for the many anecdotal observations of physical and mental stress affecting disease course. In previous studies of a neoplastic lymphokine-responsive B cell clone, BCL1-3B3, we noted that these cells produced a lymphokine which could affect normal B cell growth and viability. Physical characterization of this lymphokine indicated that its molecular weight was identical to that of the neuroendocrine hormone adrenocorticotropin (ACTH). Since Blalock and colleagues had reported the production of ACTH by virally-infected B cells, we have investigated whether ACTH can functionally mimic the BCL1-3B3-derived lymphokine. The neuroendocrine hormone adrenocorticotropin (ACTH) can increase in vitro murine B lymphocyte proliferation when added at physiologically relevant concentrations between 10(-9) to 10(-11) M. ACTH does not mimic the action of any lymphokine known to be required for B cell proliferation such as IL-2, IL-4, or IL-5. ACTH requires the presence of one or more of these known B cell stimulatory factors for its action and the most marked increase in B cell proliferation were noted in assays for IL-5 activity where 10(-10) M ACTH increased thymidine incorporation up to five-fold. Using two-stage assays, we determined that ACTH acts during the latter stages of B cell activation (i.e., 3-4 days after initial stimulation with either the combination of IL-4, GAMIg-Sepharose, and IL-1 or the combination of DxS and IL-5). These data indicate a direct role for a stress-induced neuroendocrine hormone in modulating the course of a humoral immune response.
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PMID:Adrenocorticotropin (ACTH) functions as a late-acting B cell growth factor and synergizes with interleukin 5. 196 84

The neuropeptide alpha-melanocyte-stimulating hormone (alpha-MSH) is known to suppress cytokine-mediated inflammation. In addition, we previously found that alpha-MSH suppressed the production of the proinflammatory cytokine interferon (IFN)-gamma by antigen-stimulated primed lymph node T cells. This immunosuppressive activity of alpha-MSH on lymph node T cell cultures is similar to that of interleukin (IL)-4. To further examine the potential 'IL-4 like' activities of alpha-MSH, antigen-stimulated lymph node T cell cultures were treated with alpha-MSH in the presence of neutralizing anti-IL-4 antibodies. The enhanced production of IFN-gamma caused by the presence of anti-IL-4 alone in the T cell cultures was squelched by alpha-MSH. This demonstrated that in these cultures, alpha-MSH regulation of IFN-gamma production operates in a fashion similar to that of endogenous IL-4. Addition of exogenous IL-4 to antigen-stimulated lymph node T cell cultures did not intensify alpha-MSH down-regulation of IFN-gamma production, and the addition of alpha-MSH to IL-4-treated cultures did not further depress IFN-gamma production. These and the previous results suggest that the mechanism of alpha-MSH suppression of IFN-gamma production in the antigen-stimulated T cell cultures is similar to, but independent of, IL-4. When antigen-presenting cells (APCs) were the only cells in the antigen-stimulated T cell cultures treated with alpha-MSH, there was a significant reduction (60-70%) of APC elicitation of IFN-gamma production by untreated primed T cells.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Alpha-melanocyte-stimulating hormone suppresses antigen-stimulated T cell production of gamma-interferon. 748 33

The presence of the opioid peptides alpha- and beta-endorphin (-End) but not methionine enkephalin (Met-enk) in in vitro cultures of purified CD4+ T cells, stimulated with concanavalin A in the presence of irradiated spleen cells, resulted in a threefold stimulation of IL-2, IL-4, and IFN-gamma production. The stimulating effect was dependent on the concentration of the peptides and reached optimal values in the dose range from 10(-12) to 10(-10) M. Similar results were obtained when purified CD4+ T cells were stimulated with immobilized anti-CD3, indicating a direct effect of opioid peptides on CD4+ T cells. Moreover, in this system a twofold enhancement of IL-6, but not IL-1, secretion was observed. These stimulatory effects were not mediated through opioid receptors since the peptide fragment beta-End6-31 that lacks the N-terminal opioid receptor binding part was still stimulatory. This is in agreement with our finding that beta-End did not affect cAMP, as described for the triggering of classical opioid receptors. Experiments undertaken to reveal the mechanism of action of opioid peptides suggest an overall enhancement of lymphokine production: (1) enhancement of IL-4 production occurred also in the presence of excess IL-2; and (2) neither IL-1 receptor-antagonizing protein nor anti-IL-6 were capable to abrogate the stimulatory effect on IL-2 and IL-4 production. Finally, the presence and activity of opioid receptors in cultures of CD4+ T cells were substantiated by the fact that the opioid receptor antagonist naloxone by itself enhanced cytokine synthesis, which points to the endogenous production by lymphocytes of down-regulating opioid peptides.
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PMID:Role of opioid peptides in the regulation of cytokine production by murine CD4+ T cells. 790 6

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.
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PMID:Identification of distinct sites of beta-endorphin that stimulate lymphokine production by murine CD4+ T cells. 791 52

In the present study we show that the opioid peptide beta-endorphin (beta-End) enhances Ia expression on murine B cells in cultures of unseparated spleen cells, mediated by low concentrations of IL-4 in the absence of antigenic or mitogenic stimulation. Since this effect was not found with purified B cells and no enhancement of IL-4 receptor expression on B cells could be observed, we studied the effect of beta-End on IL-4 production. To this end, purified CD4+ T cells were stimulated with suboptimal concentrations of Con A in the presence of irradiated spleen cells. It was indeed shown that beta-End enhances IL-4 production. To establish the role of macrophages in this process, we measured IL-1 and IL-6 production under the influence of beta-End. Splenic adherent cells as well as peritoneal macrophages produced higher levels of IL-1 and IL-6 in response to beta-End, whereas IL-1 was shown to enhance Ia expression similar to beta-End. Using anti-IL-6 it was demonstrated that IL-6 was required for the stimulation of Ia expression by beta-End. It is concluded that a local increase in beta-End may result in upregulation of Ia expression on B cells, thereby most likely improving their antigen-presenting capacity.
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PMID:Beta-endorphin stimulates Ia expression on mouse B cells by inducing interleukin-4 secretion by CD4+ T cells. 809 50

A panel of long-term murine T lymphocyte clones specific for the glycoprotein of vesicular stomatitis virus (VSV) in association with either H-2I-Ad or I-E(d) was tested for the production of cytokines in both resting and poststimulation states using both in situ hybridization and bioassay. All but one of the clones showed antigen-specific cytolytic activity in a 4-hr 51Cr release assay. Unexpectedly, the clones did not appear to be typical Th1 cells. Five of these T cell clones produced both IL-2 and IFN-gamma but not IL-4 after stimulation with either phorbol 12-myristate 13-acetate (PMA) or concanavalin A (Con A). Some clones constitutively expressed mRNA for IL-2 and INF-gamma. The proliferation of these clones was factor independent, suggesting an autocrine growth mechanism. Three clones produced variable levels of IL-4 mRNA and some, to significant quantities, of IL-2 mRNA. One cytolytic clone produced neither IL-2 nor IL-4 mRNA to detectable levels, although mRNA for IFN-gamma was observed. A noncytolytic, Ag-specific clone produced IL-6, tumor necrosis factor (TNF), and lymphotoxin (LT), but no IL-2, IL-4, or IFN-gamma mRNA. There was a strong quantitative correlation between the expression of IL-2-, INF-gamma-, and LT-specific mRNAs by the clones. All the T cell clones tested which secreted INF-gamma and LT expressed no measurable IL-4 mRNA. We examined expression of several other genes in the panel of clones. These included TNF, met-enkephalin (met-enk), IL-1, and IL-6. IL-1 m-RNA synthesis was not observed in any of the T cell clones. Almost all clones produced TNF mRNA. Parallel bioassays showed that secreted IL-2/IL-4 activity levels and mRNA levels correlated well for all clones. Thus, we observed a great degree of heterogeneity among CD4+ cytolytic T lymphocyte clones.
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PMID:Lymphokine expression profile of resting and stimulated CD4+ CTL clones specific for the glycoprotein of vesicular stomatitis virus. 838 Oct 52

alpha-Melanocyte-stimulating hormone (alpha-MSH) is released by immunocompetent cells as well as the pituitary gland and functions as a potent inhibitor of immune and inflammatory reactions. Therefore, it was investigated whether normal human monocytes express melanocortin (MC) receptors specific for alpha-MSH. Upon FACS analysis using biotin-labeled alpha-MSH, a low number of alpha-MSH binding sites was detectable on unstimulated monocytes. alpha-MSH receptor expression was up-regulated when monocytes were treated with endotoxin (LPS) or mitogen (PHA) for 3 to 5 days and was further augmented by the addition of cytokines such as IL-2, IFN-gamma, IL-4, and IL-10. Adrenocorticotropin, a precursor of alpha-MSH, but not the structurally unrelated beta-MSH, competitively inhibited alpha-MSH binding, suggesting that the receptor expressed on monocytes is specific for alpha-MSH. This was further confirmed by reverse transcription-PCR, which demonstrated that monocytes express mRNA specific for the MC receptor MC-1, which binds alpha-MSH and adrenocorticotropin, whereas mRNA specific for other known melanocortin receptors was not detectable. To investigate whether the immunosuppressing capacity of alpha-MSH is associated with the up-regulation of MC-1, its effect on the expression of costimulatory molecules (CD86 and CD80) on human monocytes was investigated. alpha-MSH significantly inhibited the expression of CD86 on LPS-treated monocytes, which exhibited a high density of MC-1, whereas CD80 expression was not altered. These findings indicate that human monocytes, depending on their activation and maturation state, are able to express MC-1, and up-regulation of MC-1 seems to be required to enable alpha-MSH to modulate immune responses in which costimulatory molecules play a decisive role.
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PMID:Evidence for the differential expression of the functional alpha-melanocyte-stimulating hormone receptor MC-1 on human monocytes. 912 Feb 97

We investigated the regulatory influence of several cytokines on the expression of preproenkephalin (PPE) mRNA in human peripheral blood mononuclear cells (PBMC). By use of a quantitative reverse-transcriptase-polymerase chain reaction (RT-PCR), we demonstrate that the T helper 2 cytokines IL-4 and IL-10 are more potent in upregulating PPE mRNA expression in human PBMC than the T helper 1 cytokines IL-2 and gamma-IFN. In addition, TGF-beta is also an effective inducer of PPE mRNA. TGF-beta, IL-4 and IL-10 increase the cytoplasmatic concentration of met-enkephalin in PBMC. Secretion of met-enkephalin in the culture supernatant of IL-4- or IL-10-stimulated PBMC could not be observed, but proenkephalin A-derived met-enkephalin containing peptides could be demonstrated. IL-4 and IL-10 do not induce PPE mRNA via the same pathways. We could observe that PKA is involved in IL-4 mediated PPE mRNA induction, whereas IL-10 apparently uses another route.
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PMID:T helper 2 cytokines induce preproenkephalin mRNA expression and proenkephalin A in human peripheral blood mononuclear cells. 935 52

Both constitutive and inducible interleukin-1 (IL-1) gene expressions have been described in the central nervous system, the former being associated with immunoreactive IL-1 neurons in human and rat hypothalami. While most studies have focused on the role of IL-1 as a mediator of pathological events in the brain, the cytokine of neuronal origin might also be involved in the regulation of physiological processes. In this study we used a previously validated technique to investigate the effects of classical neurotransmitters and the hypophysiotropic peptide corticotropin-releasing hormone (CRH) on the release of immunoreactive (ir) IL-1 beta from acute rat hypothalamic explants. We found that basal irIL-1 beta secretion is significantly inhibited by acetylcholine and histamine and increased by dopamine, while dexamethasone, IL-4 and IL-10 have no effect. Moreover, cytokine release is dose-dependently increased by CRH. Such effects of the neurotransmitters and CRH are observed in short-term incubation experiments, indicating that a pre-formed pool of hypothalamic IL-1 beta is involved. These findings also suggest that the interaction between IL-1, neurotransmitters and neuropeptides might play a role in the physiological regulation of such processes as body temperature, food intake and the control of hypothalamic-hypophyseal axes.
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PMID:The release of immunoreactive interleukin-1 beta from rat hypothalamic explants is modulated by neurotransmitters and corticotropin-releasing hormone. 942 15


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