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)

Treatment of splenic leukocytes from Cornell K strain male chickens (homozygous at the B15 locus of the major histocompatibility complex) with ovine corticotropin-releasing factor (oCRF), before their co-incubation with naive chicken adrenal cells, resulted in an increase in corticosterone production. Supernatants from the oCRF-treated splenic leukocytes caused a time-dependent increase in corticosterone production when incubated with chicken adrenal cells. Adding oCRF directly to chicken adrenal cells did not increase corticosterone production. Pretreatment of peripheral leukocytes with oCRF increased their activity in a concanavalin A mitogen assay. Thus, chicken leukocytes stimulated with corticotropin releasing factor appear to increase the production of an "adrenocorticotropin-like" substance (adrenocorticotropin-like because it increases corticosterone production by adrenal cells), and increased their cell-mediated immune activity.
 ...
PMID:Ovine corticotropin-releasing factor increases endocrine and immunologic activity of avian leukocytes in vitro. 184 36

To investigate the requirements for induction of cytotoxic T lymphocytes (CTL) by peptides we chose the 16-residue nucleoprotein peptide (NPP; 365-380) from the influenza virus A/NT/60/68 as model substrate that is recognized in conjunction with major histocompatibility complex H-2d. Here we present that CTL can be raised from naive animals by repeated in vitro stimulation with high concentrations of peptide. The frequency of this response can be boosted by immunization of the animals with NPP-conjugated to ovalbumin as a carrier. However, in contrast to NPP-specific CTL lines raised from virus-primed animals none of the peptide-induced CTL lines were able to lyse virus-infected targets. Although they did not show an apparent difference in fine specificity of the peptide recognized, their affinity to the target cells was 100-fold lower than that of CTL from virus-primed animals as estimated from the peptide concentration needed to achieve significant lysis. In addition, the activity of peptide-induced CTL was very sensitive to blocking by anti-CD8 antibodies as compared to virus-specific CTL. Furthermore, all peptide-induced CTL showed a high second reactivity for allogeneic H-2k targets. Therefore, it is argued that high epitope density achieved by high peptide concentrations can in vitro recruit lymphocytes of another specificity. For the tested peptide the reactive T lymphocytes showed high alloreactivity.
 ...
PMID:Recruitment of alloreactive cytotoxic T lymphocytes by an antigenic peptide. 248 86

The S region of the murine major histocompatibility complex contains two structurally related genes (21-OHase A and 21-OHase B) that encode 21-hydroxylase (21-OHase), an enzyme essential for the synthesis of adrenal steroids. Expression of these two genes has been analyzed by using oligonucleotide probes specific for the 21-OHase A and B genes and by DNA-mediated gene transfer. Hybridization of the oligonucleotides to blots of BALB/c adrenal RNA demonstrated that all 21-OHase mRNA is derived from the 21-OHase A gene. Cosmids bearing either the 21-OHase A or B gene were introduced into Y1 adrenocortical tumor cells by cotransfection with pSV2-neo. Cells transfected with the 21-OHase A gene expressed 21-OHase as determined by steroid metabolism and by RNA blot hybridization; 21-OHase transcripts were not detected in parent Y1 cells or in cells transfected with the 21-OHase B gene. Treatment of 21-OHase A transfectants with adrenocorticotropin increased 21-OHase mRNA levels by up to 10-fold, thus mimicking the observed effect of this hormone on 21-OHase levels in primary adrenal cultures. The regulated expression of the 21-OHase A gene in transfected Y1 cells should provide a useful system for the investigation of factors controlling the adrenal-specific regulation of 21-OHase activity.
 ...
PMID:Expression of murine 21-hydroxylase in mouse adrenal glands and in transfected Y1 adrenocortical tumor cells. 299 80

The mechanism of presentation of foreign antigens to helper T lymphocytes and the nature of the structures involved in this process are not totally understood. It is well documented that this event is carried out by antigen-presenting cells (APC) (e.g., macrophages, dendritic cells, and B lymphocytes) that internalize the antigen, process it, reexpress it on their membrane surface, and present it to the T cell in the context of major histocompatibility complex class II (Ia) molecules. Recent evidence supports the hypothesis that peptide antigens associate directly with Ia molecules on the APC surface membrane. However, the characteristics of other APC membrane structures potentially involved in antigen presentation are not entirely clear. Previous studies in our laboratories identified a guinea pig macrophage membrane-bound, non-Ia-containing antigenic complex (peak A) formed upon incubation of APC with the octapeptide antigen angiotensin (AII). This complex was capable of stimulating AII-immune guinea pig T cells and thus appeared to contain the immunologically relevant form of the antigen. For this reason it was important to establish whether such complex formation with peptides occurs with other cell types and with other peptide antigens. In the present study we found that other types of cells are also capable of forming such a membrane complex with antigen (peak A) and that this event is not unique to AII. Two other peptides, alpha-melanocyte-stimulating hormone and human fibrinopeptide B, both of which are antigenic in mice, were found to form peak A with a number of murine cell lines. As in our earlier studies with guinea pig macrophages, there was no evidence from these experiments for a role for major histocompatibility complex Ia antigens in the peptide binding observed. Differences in both the amount of peak A formation and the pattern of peptide antigen degradation were found from cell line to cell line for a given peptide, and from peptide to peptide for a given cell line, suggesting cellular heterogeneity in peptide processing and retention. In addition, cross-inhibition studies indicated that there was peptide specificity in the formation of peak A perhaps suggestive of molecular heterogeneity in the structure of peak A. These results indicate that there may be several types of cell surface molecules that specifically bind and retain peptide antigens.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:Heterogeneity in cellular antigen retention structures. 368 Sep 48

Adaptation of the adrenal gland to the demands of the organism is regulated functionally and structurally. Three common hypotheses on zonation in the adrenal gland, the migrational, zonal, and transformation field theories, try independently to reconcile the findings on structure, proliferation, and cell death. The classical theories on zonation are revisited in the light of recent data on cell death and renewal. In accordance with data on cell death as immunoreactivity against FAS(CD 95), an apoptosis-inducing receptor, in situ end labelling of fragmented DNA, and ultrastructural analyses, programmed cell death (PCD) occurs throughout the whole organ. The angiotensin II receptor subtypes described in the adrenal allow an additional regulation of tissue homeostasis by proliferative and even by the antiproliferative effects of the angiotensin II type 2 receptor. Proto-oncogenes are involved in the regulation of cell cycle and PCD, and adrenocorticotropin asserts its tissue integrating and differentiating effects by regulating proto-oncogenes such as c-jun, c-fos, jun-B and c-myc. Polypeptides involved in proliferation and DNA repair, such as proliferating cell nuclear antigen and Ki-67, have been found within zones of expected cell senescence. The expression of the class II major histocompatibility complex on normal adrenocortical cells allows cell-to-cell communication with the immune system and may trigger the Fas/Fas-ligand system to permit tissue regression and decreasing activity in both systems. In summary, new data allow us to reappraise and to reconcile the classical theories. Apoptosis is a physiological process in the adrenal gland. There is a differential regulation of apoptosis in the different zones. An investigation of this process may elucidate the basic mechanisms of adrenal zonation.
 ...
PMID:Tissue remodelling in the adrenal gland. 969 69

The recognition requirements necessary for murine alloreactive cytotoxic T-cells to carry out their effector function has been investigated using target cells that express a unique class I major histocompatibility complex (MHC)-peptide pair. The human cell line T2 and the murine cell line RMA-S are defective in peptide transport components needed to effectively express stable MHC class I molecules at the cell surface. When T2 cells were infected with a vaccinia virus that encoded the Kd gene and provided with a Kd-motif peptide from the nucleoprotein of influenza virus (NPP), these cells could be lysed by polyclonal allo Kd-reactive cytotoxic T-lymphocytes (CTL). Similar results were obtained with the murine RMA-S-Kd cell line, transfected with cDNA able to express some 'empty' Kd that is heat-labile. Adding another Kd-motif peptide from influenza virus haemagglutinin (HAP) stabilized the surface expression of Kd and allowed the RMA-S-Kd cells to be lysed before or after heat shock. At 27 degrees C anti-Kd alloreactive CTL-lysed target cells in the presence and absence of HAP peptide. Alloreactive CTL appear to have a more stringent requirement for a high density of MHC class I on cell surfaces relative to peptide-specific MHC-restricted CTL. We conclude that while Kd-restricted CTL activity is strictly peptide-specific, anti-Kd-specific alloreactivity is MHC allele-specific, but peptide-nonspecific. This conclusion is at odds with the Standard Model of T-cell receptor (TCR) function, but consistent with the predictions of a Competing Model of TCR function.
 ...
PMID:Alloreactive cytotoxic T-cell function, peptide nonspecific. 1035 67

Oral hormone substitution for the treatment of Addison's disease inadequately replaces the physiologic circadian secretion of corticosteroids. Alternative therapeutic approaches are reimplantation of healthy autologous adrenal tissue and allogeneic transplantation (Tx), respectively. The aim of our study was to evaluate the functional capacity of adrenal grafts and the influence of intercellular adhesion molecule-1 (ICAM-1) on graft survival. Fragmented adrenal glands of wild-type B10.BR (H-2k) and wild-type or ICAM-1-deficient BALB/c (H-2d) mice were transplanted underneath the kidney capsule of adrenalectomized B10.BR mice [complete major histocompatibility complex (MHC) haplotype disparity in the latter]. Postoperatively, the endocrine function of the adrenal grafts was evaluated by the following parameters: (1) survival analysis of the recipients (termination at day 70 after Tx); (2) reverse transcription-polymerase chain reaction expression analysis of aldosterone synthase (zona glomerulosa-specific) and of 11b-hydroxylase (zona fasciculata-specific); and (3) measurement of basal adrenocorticotropic hormone (ACTH) stimulated serum corticosterone levels. Expression of both enzyme-specific mRNAs was detected in the grafts at any time during the post-Tx period. The adrenal grafts of syngeneic and surviving MHC-disparate mice displayed a similar basal hormone secretion, which was about 60% lower than that in sham-operated animals. In the transplanted mice, ACTH-stimulated corticosterone measurement revealed a 5- to 10-fold decreased functional reserve capacity. ICAM-1 deficiency significantly prolonged the survival of adrenal grafts. Fragmented adrenal grafts are able to maintain physiologic basal corticosterone levels but had markedly reduced reserve capacity. Nevertheless, the results give rise to hopes that autologous or MHC-compatible allogeneic transplantation of adrenal grafts may replace oral hormone substitution in humans.
 ...
PMID:Transplantation of adrenal tissue fragments in a murine model: functional capacities of syngeneic and allogeneic grafts. 1201 74

The collapse of major histocompatibility complex (MHC) class-I-dependent immune privilege can lead to autoimmune disease or fetal rejection. Pragmatic and instructive models are needed to clarify the as yet obscure controls of MHC class I down-regulation in situ, to dissect the principles of immune privilege generation, maintenance, and collapse as well as to develop more effective strategies for immune privilege restoration. Here, we propose that human scalp hair follicles, which are abundantly available and easily studied, are ideally suited for this purpose: interferon-gamma induces ectopic MHC class I expression in the constitutively MHC class-I-negative hair matrix epithelium of organ-cultured anagen hair bulbs, likely via interferon regulatory factor-1, along with up-regulation of the MHC class I pathway molecules beta(2)microglobulin and transporter associated with antigen processing (TAP-2). In the first report to identify natural immunomodulators capable of down-regulating MHC class I expression in situ in a normal, neuroectoderm-derived human tissue, we show that ectopic MHC class I expression in human anagen hair bulbs can be normalized by treatment with alpha-MSH, IGF-1, or TGF-beta1, all of which are locally generated, as well as by FK506. These agents are promising candidates for immune privilege restoration and for suppressing MHC class I expression where this is clinically desired (eg, in alopecia areata, multiple sclerosis, autoimmune uveitis, mumps orchitis, and fetal or allograft rejection).
 ...
PMID:Collapse and restoration of MHC class-I-dependent immune privilege: exploiting the human hair follicle as a model. 1474 67

Superantigens (SAgs) activate the immune system by stimulating massive proliferation of T cells in a major histocompatibility complex (MHC)-dependent manner. This excessive increase in T cells results in the release of cytokines such as interleukin-2 (IL-2), interferon-gamma (IFNgamma), and tumor necrosis factor-alpha (TNFa). As an adaptive feedback mechanism, SAgs can also activate the hypothalamic pituitary adrenal (HPA) axis by stimulating the release of corticotropin releasing hormone (CRH) from the hypothalamus, adrenocorticotropic hormone (ACTH) from the anterior pituitary, and ultimately corticosterone (CORT) from the adrenal gland. Additionally, SAg exposure modifies behavior, although it has not been shown to induce malaise or decrease mobility. Some behavioral consequences include increased gustatory neophobia, neophobia to inanimate non-gustatory objects, and heightened anxiety. Cytokines such as TNFa have been shown to mediate some of these behavioral consequences as well as the endocrine and neurobiological effects of SAg exposure. The particular behavioral repertoire and cytokine profiles observed are in some cases unique to SAgs, as compared to other immune challenges such as lipopolysaccharide (LPS). Therefore, SAgs serve as a useful model to understand the behavioral, endocrine, and neurobiological effects of a T cell driven immune response.
 ...
PMID:Impact of superantigenic molecules on central nervous system function. 1927 59

Mice homozygous for the anorexia (anx) mutation are characterized by poor food intake and death by three to five weeks after birth. By P21 these mice display lower density of hypothalamic neuropeptides, including Agouti gene-related protein (AGRP). The AGRP/neuropeptide Y (NPY) system of the anx/anx mice develops normally until postnatal day (P) 12, then the normal increase in fiber density ceases, in some areas even distinctly decreases. This overlaps with activation of microglia, indicating an inflammatory and/or degenerative process. Here we studied, by in situ hybridization and immunohistochemistry (IHC), the expression of major histocompatibility complex (MHC) class I-related molecules and markers for cellular reactivity in hypothalamus of anx/anx mice. MHC class I transcript and -related proteins were found in arcuate nucleus (Arc), presumably both in neurons and glia, the latter also in areas innervated by AGRP (NPY) neurons. In the anx/anx hypothalamus, using TUNEL labeling, significantly higher number of apoptotic cells were found compared with +/+ mice, and active caspase 6 immunoreactivity was detected in degenerating NPY-fibers as well as signs of "microglia-associated cell death". In addition, Y1 receptor-labeled processes and soma of pro-opiomelanocortin (POMC) neurons, were markedly decreased at P21. These results support the hypothesis of degeneration of hypothalamic arcuate neuron populations in the anx/anx mice, whereby the AGRP system may be first affected, the changes in the POMC system being secondary in this process.
 ...
PMID:Evidence of hypothalamic degeneration in the anorectic anx/anx mouse. 2096 82


1