Corticotropin-Releasing Hormone Causes Vasodilation in Human Skin via Mast Cell-Dependent Pathways

Crompton, Renee; Clifton, Vicki L.; Bisits, Andrew; Read, Mark; Smith, Roger; Wright, Ian

doi:10.1210/jc.2003-030377

Cited by 86 publications

(63 citation statements)

References 43 publications

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“…CRF and its related peptides reach the inflammation site either through sensory nerve terminals or via production by local epithelium and/or by the inflammatory cells themselves. A well-established target of CRF and UCN is the mast cell (12)(13)(14)(15)(16)(17). We have previously shown that CRF also affects monocytes/macrophages by augmenting LPS-induced cytokine production (11).…”

Section: Discussionmentioning

confidence: 99%

“…CRF acts as an ad hoc proinflammatory factor because blockade of its effect by specific anti-CRF serum or CRF antagonists attenuates the inflammatory response in several models of inflammation including that of carrageenin, turpentine, and Gram-negative bacterial LPS-induced inflammation (9 -11). A well-defined immune target of CRF is the mast cell (12)(13)(14)(15)(16)(17). Indeed, mast cells express the CRF and the CRF-related protein urocortin (UCN) 1 and possess their specific binding sites (18).…”

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confidence: 99%

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Corticotropin-Releasing Factor and the Urocortins Induce the Expression of TLR4 in Macrophages via Activation of the Transcription Factors PU.1 and AP-1

Tsatsanis¹,

Androulidaki²,

Alissafi³

et al. 2006

The Journal of Immunology

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Corticotropin-releasing factor (CRF) augments LPS-induced proinflammatory cytokine production from macrophages. The aim of the present study was to determine the mechanism by which CRF and its related peptides urocortins (UCN) 1 and 2 affect LPS-induced cytokine production. We examined their role on TLR4 expression, the signal-transducing receptor of LPS. For this purpose, the murine macrophage cell line RAW 264.7 and primary murine peritoneal macrophages were used. Exposure of peritoneal macrophages and RAW 264.7 cells to CRF, UCN1, or UCN2 up-regulated TLR4 mRNA and protein levels. To study whether that effect occurred at the transcriptional level, RAW 264.7 cells were transfected with a construct containing the proximal region of the TLR4 promoter linked to the luciferase gene. CRF peptides induced activation of the TLR4 promoter, an effect abolished upon mutation of a proximal PU.1-binding consensus or upon mutation of an AP-1-binding element. Indeed, all three peptides promoted PU.1 binding to the proximal PU.1 site and increased DNA-binding activity to the AP-1 site. The effects of CRF peptides were inhibited by the CRF2 antagonist anti-sauvagine-30, but not by the CRF1 antagonist antalarmin, suggesting that CRF peptides mediated the up-regulation of TLR4 via the CRF2 receptor. Finally, CRF peptides blocked the inhibitory effect of LPS on TLR4 expression. In conclusion, our data suggest that CRF peptides play an important role on macrophage function. They augment the effect of LPS by inducing Tlr4 gene expression, through CRF2, via activation of the transcription factors PU.1 and AP-1.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Corticotropin-Releasing Factor and the Urocortins Induce the Expression of TLR4 in Macrophages via Activation of the Transcription Factors PU.1 and AP-1

Tsatsanis¹,

Androulidaki²,

Alissafi³

et al. 2006

The Journal of Immunology

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“…Iontophoretic coapplication of atropine (10 mM) caused a more profound reduction (27 Ϯ 8 PU; n ϭ 12; 26 Ϯ 4%; P Ͻ 0.01, paired Student's t-test). Thus our experimental procedures were working as would be predicted from previous studies (7,18), serving as positive controls for the following experiments. The response to menthol (Fig.…”

Section: Aorta Endotheliummentioning

confidence: 99%

Transient receptor potential melastatin 8 channel involvement in the regulation of vascular tone

Johnson¹,

Melanaphy²,

Purse³

et al. 2009

American Journal of Physiology-Heart and Circulatory Physiology

136

137

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Johnson CD, Melanaphy D, Purse A, Stokesberry SA, Dickson P, Zholos AV. Transient receptor potential melastatin 8 channel involvement in the regulation of vascular tone. Am J Physiol Heart Circ Physiol 296: H1868 -H1877, 2009. First published April 10, 2009 doi:10.1152/ajpheart.01112.2008.-The transient receptor potential melastatin 8 (TRPM8) channel has been characterized as a cold and menthol receptor expressed in a subpopulation of sensory neurons but was recently identified in other tissues, including the respiratory tract, urinary system, and vasculature. Thus TRPM8 may play multiple functional roles, likely to be in a tissue-and activation statedependent manner. We examined the TRPM8 channel presence in large arteries from rats and the functional consequences of their activation. We also aimed to examine whether these channels contribute to control of conscious human skin blood flow. TRPM8 mRNA and protein were detected in rat tail, femoral and mesenteric arteries, and thoracic aorta. This was confirmed in single isolated vascular myocytes by immunocytochemistry. Isometric contraction studies on endothelium-denuded relaxed rat vessels found small contractions on application of the TRPM8-specific agonist menthol (300 M). However, both menthol and another agonist icilin (50 M) caused relaxation of vessels precontracted with KCl (60 mM) or the ␣-adrenoceptor agonist phenylephrine (2 M) and a reduction in sympathetic nerve-mediated contraction. These effects were antagonized by bromoenol lactone treatment, suggesting the involvement of Ca 2ϩ -independent phospholipase A 2 activation in TRPM8-mediated vasodilatation. In thoracic aorta with intact endothelium, menthol-induced inhibition of KCl-induced contraction was enhanced. This was unaltered by preincubation with either N -nitro-L-arginine methyl ester (L-NAME; 100 nM), a nitric oxide synthase inhibitor, or the ACh receptor antagonist atropine (1 M). Application of menthol (3% solution, topical application) to skin caused increased blood flow in conscious humans, as measured by laser Doppler fluximetry. Vasodilatation was markedly reduced or abolished by prior application of L-NAME (passive application, 10 mM) or atropine (iontophoretic application, 100 nM, 30 s at 70 A). We conclude that TRPM8 channels are present in rat artery vascular smooth muscle and on activation cause vasoconstriction or vasodilatation, dependent on previous vasomotor tone. TRPM8 channels may also contribute to human cutaneous vasculature control, likely with the involvement of additional neuronal mechanisms.human; rat; artery ION CHANNELS, ESPECIALLY Ca 2ϩ -permeable channels, are of central importance to the control of vascular tone as well as long-term phenotypic remodeling. In recent years, members of the transient receptor potential (TRP) superfamily of cation channels attracted considerable interest as novel nonvoltage gated Ca 2ϩ permeable cation channels, important determinants of vascular function and disease (2, 4, 5, 13). These channels can be constitutively active or acti...

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“…CRH can also modify DNA synthesis in the dermal and epidermal compartments of cultured mouse skin depending on the phase of the hair growth cycle (24). These differential effects are apparently related to fluctuations in CRH-R1 and CRH-R2 expression during the hair growth cycle (20,24,65) Skin vasculature is a recognized target for CRH and urocortin peptides (6,(77)(78)(79), where, depending on the animal model used, CRH can induce local vascular dilatation (6,(77)(78)(79) and either inhibit or stimulate angiogenesis (80,81). Interestingly, both CRH and urocortin demonstrated anti-edema effects (82)(83)(84).…”

Section: Phenotypic Effects Of Crh and Urocortin In Cultured Skin Cellsmentioning

confidence: 99%

“…Interestingly, both CRH and urocortin demonstrated anti-edema effects (82)(83)(84). In the specific case of human skin, Clifton et al clearly have shown vasodilatory action of CRH, mediated by mechanisms that included both indirect effects, activation of mast cells or endothelial-dependent pathways, and a direct action on the blood vessel wall (77)(78)(79). These vascular effects of CRH appear to be dependent on the local level of estrogenization (77).…”

Section: Phenotypic Effects Of Crh and Urocortin In Cultured Skin Cellsmentioning

confidence: 99%

Corticotropin releasing hormone and the skin

Słomiński¹

2006

Front Biosci

139

228

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Cotricotropin-releasing hormone (CRH) and related peptides are produced in skin that is dependent on species and anatomical location. Local peptide production is regulated by ultraviolet radiation (UVR), glucocorticoids and phase of the hair cycle. The skin also expresses the corresponding receptors (CRH-R1 and CRH-R2), with CRH-R1 being the major receptor in humans. CRH-R1 is expressed in epidermal and dermal compartments, and CRH-R2 predominantly in dermal structures. The gene coding for CRH-R1 generates multiple isoforms through a process modulated by UVR, cyclic adenosine monophosphate (cAMP) and phorbol 12-myristate 13-acetate. The phenotypic effects of CRH in human skin cells are largely mediated by CRH-R1alpha through increases in concentrations of cAMP, inositol triphosphate (IP 3 ), or Ca 2+ with subsequent activation of protein kinases A (PKA) and C (PKC) dependent pathways. CRH also modulates the activity of nuclear factor of kappa light polypeptide gene enhancer in B-cells (NF-kappaB), activator protein 1 (AP-1) and cAMP responsive element binding protein (CREB). The cellular functions affected by CRH depend on cell type and nutritional status and include modulation of differentiation program(s), proliferation, viability and immune activity. The accumulated evidence indicates that cutaneous CRH is also a component of a local structure organized similarly to the hypothalamo-pituitary-adrenal axis. KeywordsHuman Skin; Hormone; Corticotropin; CRH; CRH-R1; CRH-R2; Urocortin; Review INTRODUCTIONCRH is the central trigger of HPA axis, and together with related peptides urocortin I-III also regulate behavioral, autonomic, endocrine, reproductive, cardiovascular, gastro-intestinal, metabolic and immune systemic functions (1-11). Other actions include local immunomodulatory (predominantly proinflammatory) effects (12)(13)(14), differing from a central immunosuppressive activity (through the HPA axis) (3). Of note, locally produced CRH can directly regulate steroid hormone production by adrenals and gonads (1,2). Furthermore, CRH in the immune cells can induce production and release of proopiomelanocortin (POMC) derived adrenocorticotropin (ACTH) and beta-endorphin peptides. NIH Public Access Author ManuscriptFront Biosci. Author manuscript; available in PMC 2007 April 2. Published in final edited form as:Front Biosci. ; 11: 2230-2248. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author ManuscriptIn vertebrates these peptides interact with membrane-bound CRH-R1 and CRH-R2 (1,2). Both receptor types belong to the group II subfamily of G protein-coupled receptors (GPCRs). CRH-R1 binds CRH and urocortin I with high affinity; it does not bind urocortin II (strescopin related protein). CRH-R2 shows preferential affinity for urocortin II, although it also binds CRH, however, with lower affinity than CRH-R1. Signal transduction through CRH-Rs is coupled to the activation of adenylate cyclase (AC), phospholipase C (PLC) and calcium channels (1, 2,5,6). ALTERNATIVELY SPLICED CRH-RS ISOFORMS: AN OVER...

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Corticotropin-Releasing Hormone Causes Vasodilation in Human Skin via Mast Cell-Dependent Pathways

Cited by 86 publications

References 43 publications

Corticotropin-Releasing Factor and the Urocortins Induce the Expression of TLR4 in Macrophages via Activation of the Transcription Factors PU.1 and AP-1

Corticotropin-Releasing Factor and the Urocortins Induce the Expression of TLR4 in Macrophages via Activation of the Transcription Factors PU.1 and AP-1

Transient receptor potential melastatin 8 channel involvement in the regulation of vascular tone

Corticotropin releasing hormone and the skin

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