Effect of the Corticotrophin Releasing Hormone Precursor on Interleukin-6 Release by Human Mononuclear Cells

Salas, Margarita; Brown, Oscar A.; Perone, Marcelo J.; Castro, María G.; Goya, Rodolfo G.

doi:10.1006/clin.1997.4395

Cited by 16 publications

(7 citation statements)

References 28 publications

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“…CRH could stimulate IL-1, IL-2, and IL-6 production in human mononuclear cells (Singh and Leu, 1990;Salas et al, 1997) and IL-6 and IL-11 release from human HaCaT keratinocytes (Zbytek et al, 2002). CRH binding to CRH-R1 typically activates adenylate cyclase, which leads to increased intracellular concentrations of cAMP and activation of protein kinase A (Grammatopoulos and Chrousos, 2002).…”

Section: Discussionmentioning

confidence: 99%

Corticotropin-Releasing Hormone Induces Vascular Endothelial Growth Factor Release from Human Mast Cells via the cAMP/Protein Kinase A/p38 Mitogen-Activated Protein Kinase Pathway

Cao¹,

Cetrulo²,

Theoharides³

2005

Mol Pharmacol

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Mast cells are involved in allergic reactions but also in innate immunity and inflammation. Corticotropin-releasing hormone (CRH), the key regulator of the hypothalamic-pituitary-adrenal axis, also has proinflammatory effects, apparently through mast cells. We showed recently that CRH selectively stimulates human leukemic mast cells and human umbilical cord bloodderived mast cells to release newly synthesized vascular endothelial growth factor (VEGF) without release of either preformed mediators or cytokines. This effect was mediated through the activation of CRH receptor-1 and adenylate cyclase with increased intracellular cAMP. However, the precise mechanism by which CRH induces VEGF secretion has not yet been defined. Here, we show that CRH-induced VEGF release was dose-dependently inhibited by the specific protein kinase A inhibitor N- [2-(4-bromocinnamylamino)ethyl]-5-isoquinoline (H89) or the p38 mitogen-activated protein kinase (MAPK) inhibitor 4-(4-fluorophenyl)-2-(4-methylsulfinylphenyl)-5-(4-pyridyl)1H-imidazole (SB203580) but not by the specific inhibitor 2Ј-amino-3Ј-methoxyflavone (PD98059) of mitogenactivated protein kinase kinase, the upstream kinase of the extracellular signal-regulated protein kinase (ERK) or the c-Jun N-terminal kinase (JNK) inhibitor 1,9-pyrazoloanthrone anthra-(1,9-cd)pyrazol-6(2H)-one (SP600125). Furthermore, CRH significantly increased protein kinase A activity, which could be mimicked by the cell-permeable cAMP analog 8-bromo-cAMP, and was blocked by H89 or the adenylate cyclase inhibitor 9-(tetrahydro-2-furanyl)-9H-purine-6-amine (SQ22536). CRH also induced rapid phosphorylation of p38 MAPK, which was mimicked by 8-bromo-cAMP and was inhibited by H89 or SB203580. CRH did not stimulate ERK or JNK phosphorylation and did not increase intracellular calcium levels. These results indicate that CRH induces VEGF release in human mast cells via selective activation of the cAMP/protein kinase A/p38 MAPK signaling pathway, thereby providing further insight into the molecular mechanism of how CRH affects the release of a key proinflammatory mediator.Corticotropin-releasing hormone (CRH), mainly produced in hypothalamus, is a 41 amino acid peptide that regulates endocrine and behavioral responses to stress through the activation of the hypothalamic-pituitary-adrenal axis, which down-regulates immune responses (Karalis et al., 1997).CRH, however, is also secreted peripherally and has proinflammatory effects possibly mediated through stimulation of mast cells (Theoharides et al., 1998). The cellular effects of CRH are initiated by the binding and activation of two main types of receptors, CRH-R1 and CRH-R2, which belong to G protein-coupled seven-transmembrane receptors (Grammatopoulos and Chrousos, 2002;Wiesner et al., 2003). We showed recently that mast cells express CRH-R1, the stimulation of which by CRH leads to the selective release of vascular endothelial growth factor (VEGF) through the acti-

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Section: Discussionmentioning

confidence: 99%

Corticotropin-Releasing Hormone Induces Vascular Endothelial Growth Factor Release from Human Mast Cells via the cAMP/Protein Kinase A/p38 Mitogen-Activated Protein Kinase Pathway

Cao¹,

Cetrulo²,

Theoharides³

2005

Mol Pharmacol

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“…For example both TNF-α and IL-1β stimulate production of CRH (Dudley, 1999) and conversely CRH inhibits the production of IL-1 and IL-6 by peripheral blood mononuclear cells (Salas et al, 1997). CRH may reduce the cytotoxicity of natural killer cells (Irwin et al, 1990) and also inhibits T cell proliferation (Jain et al, 1991).…”

Section: Page 13 Of 24mentioning

confidence: 99%

Endocrine immune interactions in human parturition

Golightly

Jabbour

Norman

2011

Molecular and Cellular Endocrinology

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Human parturition is an inflammatory event, modulated and influenced by a host of other environmental and physiological processes, including the endocrine hormones.Complex bidirectional communication occurs between the two systems to bring about some of the changes that are seen in labour, an event that is not yet fully understood.Preterm birth is a major problem in obstetrics and neonatology, with dysfunctional labour or prolonged pregnancy also making increasingly significant contributions to maternal morbidity. With better understanding of normal and abnormal parturition we may be able to develop novel ways of treating these complications of pregnancy and reduce maternal and neonatal morbidity and mortality. This review discusses the crucial role that endocrine-immune interaction plays in the process of labour and in the processes of abnormal and preterm labour. We propose that amongst these complex interactions it is the immune system that is the driving force behind human parturition. Keywords Parturition Endocrine InflammationImmune

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“…Given that we have previously shown that the CRH precursor itself is biologically active [7, 29, 30], it is likely that both the full-length CRH precursor and its cleavage product, CRH (1–41), elicited ACTH release from anterior pituitary cells. We do not discount that proCRH intermediate metabolites, as shown eluting between ∼18 and 4.75 kD in the COS-7 cell chromatogram, might also contribute to the ACTH-releasing activity elicited by the conditioned media.…”

Section: Discussionmentioning

confidence: 99%

“…However, no CRH-containing proCRH metabolites were indicated in the Western blots in this study. The intermediate metabolite, proCRH 93–187 [30], has a molecular size of approximately 9.5 kD and may be too small to be visualized adequately under the conditions used for Western blotting. Alternatively, it is possible that our CRH antibody does not recognize this proCRH intermediate in Western blots.…”

Section: Discussionmentioning

confidence: 99%

Generation of a Recombinant Herpes Simplex Virus Type 1 Expressing the Rat Corticotropin- Releasing Hormone Precursor: Endoproteolytic Processing, Intracellular Targeting and Biological Activity

Tomašec

Preston²,

Linton³

et al. 1999

Neuroendocrinology

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We describe the generation of a recombinant herpes simplex virus type 1 (HSV1) vector, tsK/CRH10, derived from the temperature-sensitive mutant tsK, expressing rat pre-procorticotropin-releasing hormone (ppCRH). In hypothalamic neurons, within the paraventricular and supraoptic nuclei, this neuropeptide precursor is processed to mature CRH (1–41), the key modulator of the hypothalamic-pituitary-adrenal stress response. We used the recombinant HSV1 tsK/CRH10 to study posttranslational processing, intracellular localization and biological activity of proCRH (pCRH) within neuronal, glial and epithelial cell lines. We showed that CRH-like immunoreactivity expressed in neuronal, glial and epithelial cells infected with tsK/CRH10 was biologically active, could be detected intracellularly and was also secreted. Our data also show that within Neuro2a and NG115 cells, the CRH precursor is cleaved to yield a CRH-like immunoreactive fragment of approximately 4.75 kD which could account for mature CRH (1–41). No endoproteolytic processing of the precursor takes place within the astrocytic 1321 NI cell line. Using immunocytochemistry techniques we detected CRH-like immunoreactivity within the endoplasmic reticulum-Golgi region in all cells and within secretory vesicles of Neuro2a and NG115 cells, suggesting correct targeting to the regulated secretory pathway within these cells. Our results demonstrate that the HSV1 recombinant vector expressing the full-length CRH precursor molecule constitutes an excellent delivery system for both cell lines and postmitotic neurons in vitro, which has enabled the study of targeting, endoproteolytic processing and biological activity of this neuropeptide precursor. Furthermore, it can also be used to generate transient transgenesis of the CRH precursor in vivo, to study neuroendocrine-immune interactions within the mammalian central nervous system.

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Effect of the Corticotrophin Releasing Hormone Precursor on Interleukin-6 Release by Human Mononuclear Cells

Cited by 16 publications

References 28 publications

Corticotropin-Releasing Hormone Induces Vascular Endothelial Growth Factor Release from Human Mast Cells via the cAMP/Protein Kinase A/p38 Mitogen-Activated Protein Kinase Pathway

Corticotropin-Releasing Hormone Induces Vascular Endothelial Growth Factor Release from Human Mast Cells via the cAMP/Protein Kinase A/p38 Mitogen-Activated Protein Kinase Pathway

Endocrine immune interactions in human parturition

Generation of a Recombinant Herpes Simplex Virus Type 1 Expressing the Rat Corticotropin- Releasing Hormone Precursor: Endoproteolytic Processing, Intracellular Targeting and Biological Activity

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