Peripheral corticotropin-releasing hormone and urocortin in the control of the immune response

Baigent, S

doi:10.1016/s0196-9781(01)00395-3

Cited by 109 publications

(73 citation statements)

References 124 publications

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“…The possible leakage of CRF from the brain to the periphery during stress is supported by the demonstration of active CRF transport from the brain to the periphery (22). However, CRF and Ucn are expressed in the GI tract (9,12,16,25) and immune cells (2). There is also preliminary evidence from PCR analysis that high levels of selective CRF 2 ligands are expressed in the stomach (12), supporting the possibility that CRF-related peptides may act through local nonhormonal mechanisms as reported for other peripheral actions of CRF (2,28).…”

Section: Discussionmentioning

confidence: 97%

“…Mouse Ucn II shares 76% identity with the 38 amino acid putative mature human Ucn (hUcn) II, 42% with rUcn, and 34% with h/rCRF (16,32). Ucn II and Ucn III from mouse or human origin display selective binding to CRF 2 and are postulated to be endogenous ligands for CRF 2 (16,32). So far little is known about the biological actions of Ucn II except for one report (32) showing that mouse Ucn II injected into the lateral brain ventricle decreased food intake without altering gross motor activity in rats.…”

mentioning

confidence: 99%

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Human urocortin II, a new CRF-related peptide, displays selective CRF₂-mediated action on gastric transit in rats

Million

Maillot

Saunders

et al. 2002

American Journal of Physiology-Gastrointestinal and Liver Physi

101

129

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Human urocortin (hUcn) II is a new member of the corticotropin-releasing factor (CRF) family that selectively binds to the CRF2 receptor. We investigated the CRF receptors involved in mediating the effects of hUcn II and human/rat CRF (h/rCRF) on gut transit. Gastric emptying, 4 h after a solid meal, and distal colonic transit (bead expulsion time) were monitored simultaneously in conscious rats. CRF antagonists were given subcutaneously 30 min before intravenous injection of peptides or partial restraint (for 90 min). hUcn II (3 or 10 g/kg iv) inhibited gastric emptying (by 45% and 55%, respectively) and did not influence distal colonic transit. The CRF2 peptide antagonist astressin2-B blocked hUcn II action. h/rCRF, rat Ucn, and restraint delayed gastric emptying while accelerating distal colonic transit. The gastric response to intravenous h/rCRF and restraint was blocked by the CRF2 antagonist but not by the CRF1 antagonist CP-154,526, whereas the colonic response was blocked only by CP-154,526. None of the CRF antagonists influenced postprandial gut transit. These data show that intravenous h/rCRF and restraint stress-induced delayed gastric emptying involve CRF2 whereas stimulation of distal colonic transit involves CRF1. The distinct profile of hUcn II, only on gastric transit, is linked to its CRF2 selectivity. partial restraint; gastric emptying; distal colonic transit; CP-154,526; astressin2-B

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Section: Discussionmentioning

confidence: 97%

mentioning

confidence: 99%

Human urocortin II, a new CRF-related peptide, displays selective CRF₂-mediated action on gastric transit in rats

Million

Maillot

Saunders

et al. 2002

American Journal of Physiology-Gastrointestinal and Liver Physi

101

129

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“…Compared with the proinflammatory role of CRH in peripheral tissues, the role of Ucn appears to be less clear (13,14). In vitro, Ucn and UcnII mediate anti-inflammatory effects by causing macrophage apoptosis (15) and stimulate the production of IL-6, which has immunomodulatory effects, in aortic smooth muscle cells (16), via CRHR2 activation.…”

mentioning

confidence: 99%

“…The presence of CRHR2 on resident and circulating immune cells such as granulocytes, monocytes, plasma, and mast cells (14,25,26) and its up-regulation on intestinal plasma cells and macrophages in patients with ulcerative colitis (22), along with the altered susceptibility of CRH-deficient mice to inflammatory (27)(28)(29) and autoimmune conditions (30), prompted us to examine intestinal inflammatory responses in CRHR2-null mice. For that purpose, we applied the C. difficile toxin A-mediated mouse model of acute intestinal inflammation, which has been previously used by us to demonstrate a peripheral proinflammatory role for CRH (29,31) mediated, at least in part, by CRHR1 (31).…”

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confidence: 99%

Corticotropin-Releasing Hormone Receptor 2-Deficient Mice Have Reduced Intestinal Inflammatory Responses

Kokkotou

Torres

Moss

et al. 2006

The Journal of Immunology

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Corticotropin-releasing hormone (CRH) and urocortins (Ucn) bind with various affinities to two G-protein-coupled receptors, CRHR1 and CRHR2, which are expressed in brain and in peripheral tissues, including immune cells. CRHR2-deficient mice display anxiety-like behavior, hypersensitivity to stress, altered feeding behavior and metabolism, and cardiovascular abnormalities. However, the phenotype of these mice in inflammatory responses has not been determined. In the present study we found that compared with wild-type CRHR2-null mice developed substantially reduced intestinal inflammation and had lower intestinal mRNA expression of the potent chemoattractants keratinocyte chemokine and monocyte chemoattractant protein 1 following intraluminal exposure to Clostridium difficile toxin A, a potent enterotoxin that mediates antibiotic-associated diarrhea and colitis in humans. This effect was recapitulated by administration of astressin 2B, a selective CRHR2 antagonist, before toxin A exposure. Moreover, Ab array analysis revealed reduced expression of several inflammatory chemokines, including keratinocyte chemokine and monocyte chemoattractant protein 1 in toxin A-exposed mice pretreated with astressin 2B. Real-time RT-PCR of wild-type mouse intestine showed that only UcnII, but not other Ucn, was significantly up-regulated by ileal administration of toxin A at 4 h compared with buffer exposure. We also found that human colonic epithelial HT-29 cells express CRHR2α mRNA, whereas expression of β and γ spliced variants was minimal. Moreover, treatment of HT-29 cells with UcnII, which binds exclusively to CRHR2, stimulated expression of IL-8 and monocyte chemoattractant protein 1. Taken together, these results provide direct evidence that CRHR2 mediates intestinal inflammatory responses via release of proinflammatory mediators at the colonocyte level.

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“…I t is now well-established that corticotropin-releasing factor (CRF) 4 and its related peptides affect the inflammatory response in a paracrine/autocrine manner (1)(2)(3)(4)(5)(6)(7)(8). 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).…”

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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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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Peripheral corticotropin-releasing hormone and urocortin in the control of the immune response

Cited by 109 publications

References 124 publications

Human urocortin II, a new CRF-related peptide, displays selective CRF₂-mediated action on gastric transit in rats

Human urocortin II, a new CRF-related peptide, displays selective CRF₂-mediated action on gastric transit in rats

Corticotropin-Releasing Hormone Receptor 2-Deficient Mice Have Reduced Intestinal Inflammatory Responses

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

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Peripheral corticotropin-releasing hormone and urocortin in the control of the immune response

Cited by 109 publications

References 124 publications

Human urocortin II, a new CRF-related peptide, displays selective CRF2-mediated action on gastric transit in rats

Human urocortin II, a new CRF-related peptide, displays selective CRF2-mediated action on gastric transit in rats

Corticotropin-Releasing Hormone Receptor 2-Deficient Mice Have Reduced Intestinal Inflammatory Responses

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

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Human urocortin II, a new CRF-related peptide, displays selective CRF₂-mediated action on gastric transit in rats

Human urocortin II, a new CRF-related peptide, displays selective CRF₂-mediated action on gastric transit in rats