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Regulation of corticotropin‐releasing hormone receptor‐2 expression in human cord blood‐derived cultured mast cells
Abstract
Corticotropin-releasing hormone (CRH) is secreted under stress and regulates the hypothalamic-pituitary-adrenal (HPA) axis; it is also secreted outside the brain where it exerts proinflammatory effects, possibly through mast cell activation. Mast cells are necessary for allergic reactions, but are increasingly implicated in acquired immunity and inflammatory diseases worsened by stress. Acute stress and intradermal CRH induced murine skin mast cell activation and increased vascular permeability that was absent in W/Wv mast cell deficient mice. The presence of functional CRH receptors (CRH-R) was recently reported on human mast cells. Here, we studied the expression of CRH-R1 and CRH-R2 by semiquantitative reverse transcriptase-polymerase chain reaction (RT-PCR) and fluorescent immunocytochemistry in human umbilical cord blood-derived cultured mast cells (hCBMCs) treated with Interleukin (IL)-1, IL-4 or lipopolysaccharide (LPS). Ten week-old hCBMCs cultured in the presence of Stem cell factor (SCF) and IL-6 were positive for both CRH-R1 and CRH-R2. However, the expression of only CRH-R2 mRNA and protein was induced by priming hCBMCs with IL-4 for the last three weeks of culture. Further analysis of the CR-H R2 mRNA expression showed that addition of IL-1 or LPS for 6 h increased only CRH-R2 gene expression. CRH had negligible effect on IL-6 secretion from non-primed hCBMCs, but induced release from IL-4 primed cells. Interestingly, LPS alone increased IL-6 release in non-primed cells, but lost this effect in primed cells. These results further implicate mast cells and CRH in either initiating or potentiating inflammatory diseases, especially those affected by stress.
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“Indeed, mast cells express receptors for CRH 207 , 208 that may act in an antagonistic fashion. Signaling via CRH1 receptors triggers mast cell degranulation, 205 whereas signaling through CRH2 receptors does not. 209”
From Mast cell ontogeny: From fetal development to life‐long health and disease (2023) · cites this paper as [208]
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Metadata
- Authors
- Papadopoulou, N. G., Oleson, L., Kempuraj, D., Donelan, J., Cetrulo, C. L., & Theoharides, T. C.
- Affiliations
- Departments of Pharmacology and Experimental Therapeutics, 1
- Department of Obstetrics and Gynecology, Tufts-New England Medical Center, Boston, MA 02111, USA 4
- Venue
- Journal of Molecular Endocrinology
- Publisher
- Bioscientifica
- Published
- 2005-12-01
- Volume
- 35
- Issue
- 3
- Pages
- R1-R8
- ISSN
- 1479-6813
- 0952-5041
- Cited by
- 30
- References
- 0
- Language
- en
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