The sigma ligand SR 31747 prevents the development of acute graft-versus-host disease in mice by blocking IFN-γ and GM-CSF mRNA expression

Carayon, Pierre; Bouaboula, Monsif; Loubet, J.F.; Bourrié, Bernard; Petitpretre, G.; Fur, G. Le; Casellas, Pierre

doi:10.1016/0192-0561(95)00066-b

Cited by 25 publications

(28 citation statements)

References 23 publications

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“…In murine studies, treatment with sigma ligands prevented both graft-vs-host disease and delayed-type hypersensitivity granuloma formation (5). These studies indicate that sigma receptor-dependent signaling plays a role in immune-mediated responses.…”

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confidence: 74%

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IL-10 Mediates Sigma1 Receptor-Dependent Suppression of Antitumor Immunity

Zhu

Sharma

Gardner

et al. 2003

The Journal of Immunology

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Sigma receptors are unique endoplasmic reticulum proteins that mediate signaling for a variety of drugs. We determined the effect of sigma1 receptor agonists on immune responses in a syngeneic lung cancer model. Sigma1 receptor agonists, including cocaine, up-regulated splenocyte IL-10 mRNA and protein production in vitro in a sigma receptor-dependent, pertussis toxin-sensitive manner. In vivo, sigma1 receptor agonists promoted tumor growth and induced IL-10 at the tumor site. Increased tumor growth was prevented by administration of specific Abs to IL-10 or by administration of specific sigma1 receptor antagonists. We report that sigma1 receptor ligands, including cocaine, augment tumor growth through an IL-10 dependent mechanism.

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confidence: 74%

“…Sigma ligands have potent immunoregulatory properties including the induction of IL-10 (4) and the suppression of IFN-␥ and GM-CSF (5). In murine studies, treatment with sigma ligands prevented both graft-vs-host disease and delayed-type hypersensitivity granuloma formation (5).…”

mentioning

confidence: 99%

IL-10 Mediates Sigma1 Receptor-Dependent Suppression of Antitumor Immunity

Zhu

Sharma

Gardner

et al. 2003

The Journal of Immunology

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“…+ T-cells (94,95). Conversely to most σ drugs, haloperidol affected only the ConA-mediated response, suggesting that σ receptors might differentially regulate T-and Bcell-mediated proliferation.…”

Section: Steroids and Neurosteroids Bind Both σ 1 And σ 2 Sites In Pementioning

confidence: 99%

The Sigma1 Protein as a Target for the Non-genomic Effects of Neuro(active)steroids: Molecular, Physiological, and Behavioral Aspects

2006

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Abstract. Steroids synthesized in the periphery or de novo in the brain, so called 'neurosteroids', exert both genomic and nongenomic actions on neurotransmission systems. Through rapid modulatory effects on neurotransmitter receptors, they influence inhibitory and excitatory neurotransmission. In particular, progesterone derivatives like 3α-hydroxy-5α-pregnan-20-one (allopregnanolone) are positive allosteric modulators of the γ-aminobutyric acid type A (GABA A ) receptor and therefore act as inhibitory steroids, while pregnenolone sulphate (PREGS) and dehydroepiandrosterone sulphate (DHEAS) are negative modulators of the GABA A receptor and positive modulators of the N-methyl-D-aspartate (NMDA) receptor, therefore acting as excitatory neurosteroids. Some steroids also interact with atypical proteins, the sigma (σ) receptors. Recent studies particularly demonstrated that the σ 1 receptor contributes effectively to their pharmacological actions. The present article will review the data demonstrating that the σ 1 receptor binds neurosteroids in physiological conditions. The physiological relevance of this interaction will be analyzed and the impact on physiopathological outcomes in memory and drug addiction will be illustrated. We will particularly highlight, first, the importance of the σ 1 -receptor activation by PREGS and DHEAS which may contribute to their modulatory effect on calcium homeostasis and, second, the importance of the steroid tonus in the pharmacological development of selective σ 1 drugs.

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“…MCS, multiple cloning site; X, Xbal; S, Sad. kines interleukin (IL) 1, IL-6, and tumor necrosis factor-a , inhibit experimental acute graft-versus-host disease by blocking the production of the Thi cytokine interferon-y (Carayon et a!., 1995), and enhance the production of endotoxin-induced antiinflammatory cytokine IL-10 in vivo (Bourne et a!., 1995).…”

Section: Figmentioning

confidence: 99%

Exon‐Intron Structure, Analysis of Promoter Region, and Chromosomal Localization of the Human Type 1 σ Receptor Gene

Prasad

Li²,

Fei³

et al. 1998

Journal of Neurochemistry

157

107

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a receptor is a protein that interacts with a variety of psychotomimetic drugs including cocaine and amphetamines and is believed to play an important role in the cellular functions of various tissues associated with the endocrine, immune, and nervous systems. Here we report on the structure and organization of the human gene coding for this receptor. The gene is -~7kbp long and contains four exons, interrupted by three introns. Exon 3 is the shortest (93 bp), and exon 4 is the longest (1,132 bp). Among the introns, intron 3 is the longest ('-~1250 bp). Exon 2 codes for the single transmembrane domain present in the receptor. 5' rapid amplification of cDNA end reactions with mRNA from the JAR human trophoblast cell line have identified 56 bp upstream of the translation start codon as the initiation site for transcription. This transcription start site has been confirmed by RNase protection analysis. Structural analysis of the 5' flanking region has revealed that the gene is TATAless. This region, however, contains a CCAATC box in the reverse complement and several GO boxes that are recognition sites for SP1. There are also consensus sequences for the liver-specific transcription factor nuclear factor-i IL, for a variety of cytokine responsive factors, and for the xenobiotic responsive factor called the arylhydrocarbon receptor. Southern blot analysis of the genomic DNA from Chinese hamster-human and mouse-human hybrid cell lines and fluorescent in situ hybridization with human metaphase chromosome spreads have shown that the gene is located on human chromosome 9, band p13, a region known to be associated with different psychiatric disorders.

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The sigma ligand SR 31747 prevents the development of acute graft-versus-host disease in mice by blocking IFN-γ and GM-CSF mRNA expression

Cited by 25 publications

References 23 publications

IL-10 Mediates Sigma1 Receptor-Dependent Suppression of Antitumor Immunity

IL-10 Mediates Sigma1 Receptor-Dependent Suppression of Antitumor Immunity

The Sigma1 Protein as a Target for the Non-genomic Effects of Neuro(active)steroids: Molecular, Physiological, and Behavioral Aspects

Exon‐Intron Structure, Analysis of Promoter Region, and Chromosomal Localization of the Human Type 1 σ Receptor Gene

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