Somatostatin receptor subtype expression in cells of the rat immune system during adjuvant arthritis

Bokum, Annemieke Ten; Lichtenauer-Kaligis, Elgin G.R.; Melief, Marie-José; Koetsveld, Peter M. van; Berthou, Christian; Hagen, P. Martin van; Hofland, Leo J.; Lamberts, Steven W. J.; Hazenberg, M. P.

doi:10.1677/joe.0.1610167

Cited by 47 publications

(34 citation statements)

References 28 publications

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“…In the lung, they have been detected on lymphocytes and also on the sensory nerve terminals (13). Somatostatin receptor autoradiography has shown upregulation of somatostatin binding sites in several immunemediated diseases (36,48,49). Furthermore, plasma somatostatin level has been shown to significantly increase during the development of adjuvant-induced arthritis in the rat (16) and, according to the present results, also during endotoxininduced airway inflammation in the mouse.…”

Section: Discussionsupporting

confidence: 73%

Role of transient receptor potential vanilloid 1 receptors in endotoxin-induced airway inflammation in the mouse

Helyes¹,

Elekes²,

Németh³

et al. 2007

American Journal of Physiology-Lung Cellular and Molecular Phys

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Airways are densely innervated by capsaicin-sensitive sensory neurons expressing transient receptor potential vanilloid 1 (TRPV1) receptors/ion channels, which play an important regulatory role in inflammatory processes via the release of sensory neuropeptides. The aim of the present study was to investigate the role of TRPV1 receptors in endotoxin-induced airway inflammation and consequent bronchial hyperreactivity with functional, morphological, and biochemical techniques using receptor gene-deficient mice. Inflammation was evoked by intranasal administration of Escherichia coli lipopolysaccharide (60 l, 167 g/ml) in TRPV1 knockout (TRPV1 Ϫ/Ϫ ) mice and their wild-type counterparts (TRPV1 ϩ/ϩ ) 24 h before measurement. Airway reactivity was assessed by unrestrained whole body plethysmography, and its quantitative indicator, enhanced pause (Penh), was calculated after inhalation of the bronchoconstrictor carbachol. Histological examination and spectrophotometric myeloperoxidase measurement was performed from the lung. Somatostatin concentration was measured in the lung and plasma with radioimmunoassay. Bronchial hyperreactivity, histological lesions (perivascular/peribronchial edema, neutrophil/ macrophage infiltration, goblet cell hyperplasia), and myeloperoxidase activity were significantly greater in TRPV Ϫ/Ϫ mice. Inflammation markedly elevated lung and plasma somatostatin concentrations in TRPV1 ϩ/ϩ but not TRPV1 Ϫ/Ϫ animals. In TRPV1 Ϫ/Ϫ mice, exogenous administration of somatostatin-14 (4 ϫ 100 g/kg ip) diminished inflammation and hyperreactivity. Furthermore, in wildtype mice, antagonizing somatostatin receptors by cyclo-somatostatin (4 ϫ 250 g/kg ip) increased these parameters. This study provides the first evidence for a novel counterregulatory mechanism during endotoxin-induced airway inflammation, which is mediated by somatostatin released from sensory nerve terminals in response to activation of TRPV1 receptors of the lung. It reaches the systemic circulation and inhibits inflammation and consequent bronchial hyperreactivity.capsaicin-sensitive afferents; inflammatory airway hyperreactivity; lipopolysaccharide; myeloperoxidase activity; somatostatin THE AIRWAYS ARE DENSELY INNERVATED by capsaicin-sensitive sensory nerves (54), which play an important regulatory role in inflammatory processes via the release of sensory neuropeptides. The transient receptor potential vanilloid 1 (TRPV1) receptor, also known as capsaicin receptor, is a nonselective cation channel expressed selectively in the cell membrane of thin afferent (C and A␦) fibers, which is activated/sensitized by noxious heat and a variety of inflammatory mediators such as protons, lipoxygenase products, bradykinin, or prostaglandins (7, 9, 10, 52). Therefore, its involvement in inflammatory and nociceptive processes has become an issue with pathophysiological relevance and important scopes for drug development (7, 52). The gene of the TRPV1 receptor was successfully deleted in mice (10), which enabled the studying of the functional roles of...

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Section: Discussionsupporting

confidence: 73%

Role of transient receptor potential vanilloid 1 receptors in endotoxin-induced airway inflammation in the mouse

Helyes¹,

Elekes²,

Németh³

et al. 2007

American Journal of Physiology-Lung Cellular and Molecular Phys

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“…In addition, histological studies in this model have revealed reduction of lymphocyte infiltration in the synovium and reduced vasculitis in SRIF-treated animals. In our studies we did not observe a reduction in the severity of rat adjuvant arthritis using the SRIF analogue octreotide (ten Bokum et al, 1999b). Takeba et al has shown that SRIF at physiological concentrations inhibits the in vitro proliferation of fibroblast-like synovial cells from RA patients (Takeba et al, 1997).…”

Section: Small-molecule Ghs Has a Considerable Immune-enhancing Effeccontrasting

confidence: 62%

The role of cortistatin in the human immune system

Hagen

Dalm

Staal

et al. 2008

Molecular and Cellular Endocrinology

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Please cite this article as: van Hagen, P.M., Dalm, V.A., Staal, F., Hofland, L.J., The Role of Cortistatin in the Human Immune System, Molecular and Cellular Endocrinology (2007Endocrinology ( ), doi:10.1016Endocrinology ( /j.mce.2008 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. AbstractCortistatin (CST) is a recently described neuropeptide that shares high homology with somatostatin (somatotropin release-inhibiting factor, SRIF) and binds with high affinity to all somatostatin receptor (sst) subtypes. CST is currently known to have a widespread distribution in many human organs including the immune system. The activities specific to CST may be partially attributable to its binding to the growth hormone secretagogue (GHS) receptor (GHS-R) and the orphan Gprotein-coupled receptor MrgX2. Human immune cells produce CST, whereas macrophage lineage and activated endothelium express sst 2 , and human lymphocytes express sst 3 . The human thymus expresses sst 1,2,3 , MrgX2 and almost all immune cells express GHS-R. Moreover, at this very moment promising research with CST in experimental animal models is being performed. On the basis of these promising results, studies aiming to further evaluate the possibilities of CST as a therapeutic agent in human immune mediated inflammatory diseases are warranted.

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“…Mice and humans express ®ve different receptors for SST (SSTR 1±5 ), each encoded by separate genes (12). We showed that whole unfractionated granuloma cells, as well as T cells (Thy1.2+ or CD4+) isolated from granulomas of schistosome-infected mice, express mRNA only for SSTR 2 (5,13 (14).…”

Section: Sstr Subtype Expression In Murine Granulomasmentioning

confidence: 92%

The somatostatin immunoregulatory circuit present at sites of chronic inflammation

Weinstock

Elliott²

2000

European Journal of Endocrinology

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Somatostatin is part of an immunoregulatory circuit that helps limit interferon-g (IFNg) production at sites of chronic in¯ammation. In murine schistosomiasis, parasite eggs induce focal, chronic granulomatous in¯ammation in the liver and intestines. These granulomas produce somatostatin 1±14 and express somatostatin receptor subtype number 2 (SSTR 2 ), which is the exclusive somatostatin receptor present in this in¯ammation. Granuloma and splenic macrophages as well as macrophage cell lines make somatostatin. There appears to be no other in¯ammatory cell source of the peptide. Various in¯ammatory mediators induce this expression, whereas substance P inhibits somatostatin production. Somatostatin can suppress IFNg secretion from T cells via interaction with the SSTR 2 receptor expressed on these cells. Other cells within the granuloma also display SSTR 2 . The effect of somatostatin on these other cell types remains unknown. The thymus of normal mice has a complete somatostatin regulatory circuit. The thymic epithelial and dendritic cells make somatostatin. Like the granulomas of murine schistosomiasis, the thymus expresses only SSTR 2 . Somatostatin likely has an important role in thymic T cell education and selection.

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Somatostatin receptor subtype expression in cells of the rat immune system during adjuvant arthritis

Cited by 47 publications

References 28 publications

Role of transient receptor potential vanilloid 1 receptors in endotoxin-induced airway inflammation in the mouse

Role of transient receptor potential vanilloid 1 receptors in endotoxin-induced airway inflammation in the mouse

The role of cortistatin in the human immune system

The somatostatin immunoregulatory circuit present at sites of chronic inflammation

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