Urocortin in Human Gastric Mucosa: Relationship to Inflammatory Activity

Chatzaki, Εkaterini; Charalampopoulos, Ioannis; Leontidis, Christos; Mouzas, Ioannis; Tzardi, Maria; Tsatsanis, Christos; Margioris, Andrew N.; Gravanis, Achille

doi:10.1210/jc.2002-020853

Cited by 78 publications

(92 citation statements)

References 30 publications

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“…This notion is supported by the findings in patients with H. pylori infection [1]. When treated, these patients fall into two categories: responders and non-responders, with responders exhibiting a further increase in their Ucn levels as inflammation resolves and non-responders having no further change in their Ucn levels.…”

Section: Discussionmentioning

confidence: 57%

“…Their expression has been linked to regulation of inflammation, and may represent a powerful therapeutic target in inflammatory bowel disease. Increased Ucn 1 expression has been found to correlate with active gastritis, and patients who responded to treatment for gastritis had even higher levels of expression [1]. In the colon, CRF-R2, the only known receptor for Ucn 2 and Ucn 3, has been found to regulate visceral pain and colonic afferent signaling [8].…”

Section: Discussionmentioning

confidence: 99%

“…A growing number of studies demonstrate that the urocortins and their receptors play an important role in regulating inflammation in the GI tract of both humans and rodents [1,4,12,13]. However, basal urocortin expression throughout the GI tract has not been systematically studied.…”

Section: Introductionmentioning

confidence: 99%

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Urocortin 2 expression in the rat gastrointestinal tract under basal conditions and in chemical colitis

et al. 2007

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It is becoming increasingly evident that the urocortins (Ucns) and their receptors are involved in the initiation and development of inflammation in the gastrointestinal (GI) tract. There has not been a systematic study of the basal expression of Ucns or their receptors in the GI tract. Here, we examined basal expression of Ucn 2 and its high-affinity receptor, CRF-R2 in the rat GI tract. Ucn 2 mRNA was expressed throughout the small and large intestine. Surprisingly, CRF-R2 mRNA expression was detected in only a subset of GI regions that expressed Ucn 2. Immunohistochemical study showed that both Ucn 2 immuno-reactivity (Ucn 2-IR) and CRF-R2-IR were consistently seen in the neurons of the myenteric plexus and the nerve fibers innervating the circular muscle. By and large, Ucn 2-IR was detected in all layers, including the mucosal and the submucosal layers throughout the GI regions. In contrast, CRF-R2-IR was very low or undetectable in the mucosal layers of all regions examined. The role of Ucn 2 and CRF-R2 was then examined in a rat model of chemically-induced colitis. In the early phase of colitis, Ucn 2 mRNA levels peaked, whereas, in striking contrast, CRF-R2 mRNA expression decreased ∼2.5-fold below control levels. At the peptide level, Ucn 2-IR was specifically induced in a large population of immune cells that infiltrated the lamina propria and submucosa of the distal colon, whereas CRFR2-IR was detected in only a small fraction of infiltrated immune cells. CRF-R2-IR was dramatically reduced in the neurons of the myenteric plexus. Thus, we show, for the first time, that in the acute phase of inflammation, Ucn 2 levels are increased whereas expression levels of its only identified receptor, CRF-R2, are decreased. This suggests that Ucn 2 exerts its effects only in part via CRF-R2.

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Section: Discussionmentioning

confidence: 57%

Section: Discussionmentioning

confidence: 99%

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Urocortin 2 expression in the rat gastrointestinal tract under basal conditions and in chemical colitis

et al. 2007

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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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“…Increased levels of CRH-related neuropeptides have been found in several conditions presenting with chronic inflammation, including rheumatoid arthritis (53)(54)(55), ulcerative colitis (56,57), Helicobacter pylorirelated gastritis (58), endometriosis (59), and Hashimoto's thyroiditis (60), making them potential indications for specific treatment through CRH receptor blockade.…”

Section: Clinical Implications Of Crh-r Antagonistsmentioning

confidence: 99%

Corticotropin-releasing hormone receptor antagonists

2006

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Corticotropin-releasing hormone (CRH), CRH-related peptides, and CRH receptors play major roles in coordinating the behavioral, endocrine, autonomic, and immune responses to stress. The wide influence of the CRH system on physiological processes in both brain and periphery implicates the respective peptides in the pathophysiology of numerous disorders characterized by dysregulated stress responses. The potential use of CRH antagonists is presently under intense investigation. Selective antagonists have been used experimentally to elucidate the role of CRH-related peptides in disease processes, such as anxiety and depression, sleep disorders, addictive behavior, inflammatory disorders, acute and chronic neurodegeneration, and preterm labor.European Journal of Endocrinology 155 S85-S91

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Urocortin in Human Gastric Mucosa: Relationship to Inflammatory Activity

Cited by 78 publications

References 30 publications

Urocortin 2 expression in the rat gastrointestinal tract under basal conditions and in chemical colitis

Urocortin 2 expression in the rat gastrointestinal tract under basal conditions and in chemical colitis

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 hormone receptor antagonists

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