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Rebecca J Ainslie Institute for Regeneration and Repair, the University of Edinburgh, Edinburgh BioQuarter, Edinburgh, United Kingdom

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Ioannis Simitsidellis Institute for Regeneration and Repair, the University of Edinburgh, Edinburgh BioQuarter, Edinburgh, United Kingdom

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Phoebe M Kirkwood Institute for Regeneration and Repair, the University of Edinburgh, Edinburgh BioQuarter, Edinburgh, United Kingdom

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Douglas A Gibson Institute for Regeneration and Repair, the University of Edinburgh, Edinburgh BioQuarter, Edinburgh, United Kingdom

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androgens, control immune cell function in the womb and how this might affect women’s reproductive health. His lab uses fate-mapping techniques, transcriptomics analysis, multiparameter flow cytometry and immunohistochemistry to characterise the phenotype

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Anne H van der Spek Department of Endocrinology and Metabolism, Academic Medical Center, Amsterdam, The Netherlands

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Eric Fliers Department of Endocrinology and Metabolism, Academic Medical Center, Amsterdam, The Netherlands

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Anita Boelen Department of Endocrinology and Metabolism, Academic Medical Center, Amsterdam, The Netherlands

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the immune response ( Boutzios & Kaltsas 2000 , Klein 2006 , De Vito et al . 2011 ), and there is an extensive body of literature available on the effects of TH on various types of innate immune cells ( De Vito et al . 2011 ). However, very few of

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Anna Cinkajzlová Experimental Medicine Centre, Institute for Clinical and Experimental Medicine, Prague, Czech Republic
Institute of Medical Biochemistry and Laboratory Diagnostics, First Faculty of Medicine and General University Hospital, Charles University, Prague, Czech Republic

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Miloš Mráz Institute of Medical Biochemistry and Laboratory Diagnostics, First Faculty of Medicine and General University Hospital, Charles University, Prague, Czech Republic
Diabetes Centre, Institute for Clinical and Experimental Medicine, Prague, Czech Republic

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Martin Haluzík Institute of Medical Biochemistry and Laboratory Diagnostics, First Faculty of Medicine and General University Hospital, Charles University, Prague, Czech Republic
Diabetes Centre, Institute for Clinical and Experimental Medicine, Prague, Czech Republic

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along with a richer blood supply and innervation than SAT. It also exerts a higher capacity for glucose and lipid uptake and production of free fatty acids, has more receptors for glucocorticoids and androgens and contains more immune cells ( Ibrahim

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Milos Mraz Third Department of Medicine – Department of Endocrinology and Metabolism, General University Hospital, First Faculty of Medicine of Charles University in Prague, U nemocnice 1, 128 00 Prague 2, Czech Republic

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Martin Haluzik Third Department of Medicine – Department of Endocrinology and Metabolism, General University Hospital, First Faculty of Medicine of Charles University in Prague, U nemocnice 1, 128 00 Prague 2, Czech Republic

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-grade inflammation characterized by increased infiltration of immune cells into AT and increased production and subsequent secretion of proinflammatory factors into circulation ( Neels & Olefsky 2006 ). This review has focused on the various subsets of immune cells

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Siobhan M Donnelly
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Bao Tran Nguyen
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Scott Rhyne
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Jordan Estes
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Subrina Jesmin Department of Biology, Appalachian State University, Department of Internal Medicine, Tsukuba University, Rankin Science North Building N219, 572 River Street, Boone, North Carolina 28608, USA

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Chishimba Nathan Mowa
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epithelial cells and the whole uterine cervical tissue in general, notably the effect of VEGF on the recruitment of immune cells to the uterine cervical epithelia and lumen. Materials and methods Animals Pregnant and nonpregnant (ovariectomized) C57BL6

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S Yellayi
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MA Zakroczymski
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V Selvaraj
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VE Valli
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Ghanta V
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WG Helferich
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PS Cooke
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The soy phytoestrogen, genistein, induces thymic atrophy when administered to ovariectomized mice by injection or in the diet. Injected genistein also causes decreased humoral immunity, but the effects of genistein on cell-mediated immunity have not been addressed. Here we examined effects of injected and dietary genistein on cell-mediated immune responses. Female C57BL/6 mice (25- to 27-days-old) were ovariectomized, then placed on phytoestrogen-free feed 5 days later. Seven days after ovariectomy, they were given daily subcutaneous injections of either dimethylsulfoxide (DMSO) or genistein (8, 20, 80 mg/kg) for 28 days; some mice were given 80 mg/kg genistein plus the anti-estrogen ICI 182,780 (5 mg/kg/week). Cell-mediated immune response was tested by analyzing the delayed-type hypersensitivity (DTH) response to a hapten, 4-hydroxy-3-nitrophenyl acetyl succinimide (NP-O-SU), at the end of treatment. Reversibility of the effects of genistein was tested by measuring the DTH response in mice that were given genistein (20 or 80 mg/kg) for 28 days, then allowed to recover for 28 days. To determine if dietary genistein could affect cell-mediated immunity, mice ovariectomized as above were fed genistein at 0, 1000 or 1500 parts per million (ppm) for 28 days. There was a 46-67% decrease in the DTH response in the footpads of mice injected with 8-80 mg/kg genistein compared with controls (P<0.05 vs control for all treatment groups); these effects were reversible. On histopathological examination of the feet, there was decreased cell infiltration in genistein-treated animals compared with controls, and the numbers of CD4(+) and CD8(+) T cells in popliteal lymph nodes were reduced. The effects of genistein are mediated through both estrogen receptor (ER) and non-ER pathways, as the anti-estrogen ICI 182,780 only partially blocked the effects of genistein on the DTH response. Dietary genistein (1000 or 1500 ppm) decreased cell-mediated immunity while producing serum genistein concentrations in the physiological range for humans under certain nutritional conditions. Further work is needed to determine if dietary genistein and phytoestrogen exposure can produce effects on cell-mediated immunity in humans or other animals under various nutritional conditions.

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AM ten Bokum
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EG Lichtenauer-Kaligis
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MJ Melief
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PM van Koetsveld
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C Bruns
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PM van Hagen
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LJ Hofland
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SW Lamberts
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MP Hazenberg
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Somatostatin is a neuropeptide that is widely distributed throughout the body. It acts as a neurohormone and a neurotransmitter and may also have an immunomodulatory role. The genes for five subtypes of somatostatin receptors (sst) have been cloned, suggesting that the diverse effects of the peptide might be mediated by different receptors. We are interested in studying the role of sst ininflammation, using an animal model. Because of the up-regulation of sst expression in inflamed joints in human rheumatoid arthritis, we chose rat adjuvant arthritis as an experimental model. In order to determine which of the sst subtypes might be important in immune modulation, subtype expression in leukocytes isolated from different lymphoid tissues of the rat was studied. Also, the expression levels of the most abundantly expressed sst mRNAs in leukocytes from spleen and blood were compared in rats with adjuvantarthritis and controls, using a semi-quantitative approach. Furthermore, the effect of systemic administration of a long-acting somatostatin analogue, octreotide, which binds selectively to sst subtypes 2 and 5 (sst2 and sst5), on the incidence and the severity of rat adjuvant arthritis, was studied. The main sst expressed in cells of the rat immune system, both resting and activated, were found to be sst3 and sst4. This contrasts with the human and murine situations, in which sst2 appears to be the main subtype expressed in the immune system. No quantitative differences in sst subtype mRNA levels in leukocytes from spleen and blood were found between rats with adjuvant arthritis and controls. Finally, no effect of systemic administration of octreotide on either the incidence or severity of adjuvant arthritis in Lewis rats was found. As octreotide binds selectively to sst2 and sst5, the absence of an immunomodulatory effect of this analogue in rat adjuvant arthritis corroborates our finding that these sst subtypes are not expressed in cells of the rat immune system. In conclusion, cells of the rat immune system appear to express a spectrum of sst (sst3 and sst4) different from that found in human granulomatous and autoimmune disease (mainly sst2). Therefore, the rat adjuvant arthritis model appears to be suitable only for studying the immunomodulatory effects of somatostatin analogues which have a high affinity for sst3 and sst4, but not for studying the immunomodulatory effects of octreotide, which has a high affinity only for sst2 and sst5.

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D. J. J. Carr
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B. R. DeCosta
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C.-H. Kim
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A. E. Jacobson
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V. Guarcello
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K. C. Rice
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J. E. Blalock
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ABSTRACT

Opioid peptides have been shown to modulate various parameters of both the humoral and cellular arms of the immune system. The modulatory capacity of the peptides can often be substantially reduced in the presence of naloxone, an opioid receptor antagonist, indicating a classical ligand-receptor interaction. In order to characterize these interactions further, we investigated the characteristics of opioid receptors on a macrophage cell line, P388d1. A δ-class opioid receptor was found with an M r of 58 000. We also identified opioid receptors on MOLT-4 (T-cell) and IM-9 (B cell) cell lines as well as thymocytes and T celland B cell-enriched populations. Using the central (brain) κ-selective agonist, U-69,593, it was also determined that P388d1 cells possess κ-like opioid receptors. Scatchard analysis of the binding of [3H]U-69,593 revealed a single population of sites with a dissociation constant of 17 ± 3 (s.e.m.) nmol/l and a total number of binding sites of 53·8 ± 1·0 (s.e.m.) fmol/106 cells. Moreover, the racemic κ-selective agonist U-50,488H was able to displace 50% of [3H]U-69,593 binding at 8·0 nmol/l, whereas other opioid ligands such as [Met]-enkephalinamide (δ-selective) and [d-Ala2,N - Me - Phe4,Gly5 - ol] - enkephalin (μ - selective) were ineffective displacers of [3H]U-69,593 except at high concentrations.

Journal of Endocrinology (1989) 122, 161–168

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J. R. WALL
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P. TWOHIG
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B. CHARTIER
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A possible effect of thyroid hormones on numbers of mononuclear cells and immune reactivity has been studied in hyperthyroid and hypothyroid guinea-pigs and rats. There were no major changes in populations of blood mononuclear cells in hyperthyroid or hypothyroid animals compared with populations in euthyroid animals. Although there was some evidence for depressed cell-mediated responses to an extract of Candida (monilia) albicans in hyperthyroid rats as assessed by skin tests, this was minor, and responses in tuberculin purified protein derivative (PPD) were normal in all groups, whilst production of macrophage migration inhibition factor in response to PPD and Candida was similar in the three groups of animals. Antibody responses to sheep red blood cells, a thymic-dependent antigen, tended to be depressed in hyperthyroid and hypothyroid rats and increased in hyperthyroid and hypothyroid guinea-pigs, although this was significant only for hyperthyroid guinea-pigs 16 days after immunization. Responses to trinitrophenol-Ficoll, a thymic-independent antigen, were similar to the three groups of guinea-pigs. Thus, a major effect of excess or deficiency of thyroid hormone on immune responses to foreign antigens has not been demonstrated, although it is possible that immune reactions against thyroid antigens may be more sensitive to the effect of thyroid hormones than responses to foreign antigens.

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CV Clevenger
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DO Freier
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JB Kline
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