Corticosteroid-independent inhibition of tumor necrosis factor production by the neuropeptide urocortin

Agnello, Davide; Bertini, Riccardo; Sacco, Silvano; Meazza, Cristina; Villa, Pia; Ghezzi, Pietro

doi:10.1152/ajpendo.1998.275.5.e757

Cited by 51 publications

(59 citation statements)

References 30 publications

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“…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. In vivo, Ucn suppresses experimental autoimmune encephalomyelitis in rats (17), reduces LPS-induced serum TNF␣ and IL-1␤ levels in mice (18), and decreases mortality after cecal ligation and puncture or following injection with bacterial endotoxin (19). However, the interpretation of those studies might be complicated by the fact that Ucn can directly up-regulate glucocortocoid production, which has anti-inflammatory effects (17,18).…”

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confidence: 99%

“…In vivo, Ucn suppresses experimental autoimmune encephalomyelitis in rats (17), reduces LPS-induced serum TNF␣ and IL-1␤ levels in mice (18), and decreases mortality after cecal ligation and puncture or following injection with bacterial endotoxin (19). However, the interpretation of those studies might be complicated by the fact that Ucn can directly up-regulate glucocortocoid production, which has anti-inflammatory effects (17,18). On the other hand, UcnII treatment worsens Listeria monocytogenes infection in mice via up-regulation of .…”

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confidence: 99%

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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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confidence: 99%

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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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“…The mechanism of stimulating the secretion of Ucn-2 hormone in early HF is not clear. The previous studies indicated that an activated serum Ucn hormones were related to antiinflammatory response (reducing the interleukin and tumor necrotizing factor secretion), in exaggerated hyperadrenergic state, or as a cardioprotective role of Ucn (Ucn-1, Ucn-2 isoforms and Ucn) in HF process (12,13,27,28). The reason for the lack of the serum Ucn-2 response in the presence of moderate to severe left ventricular dysfunction (Group A) may be due to withdrawal of anti-inflammatory and cardioprotective response in HF process.…”

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confidence: 99%

Relationship of urocortin-2 with systolic and diastolic functions and coronary artery disease: an observational study

Topal¹,

Yağmur²,

Otlu³

et al. 2012

Anadolu Kardiyol Derg

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Objective: The urocortin (Ucn) hormones have many important roles in the cardiovascular system. Apart from systolic dysfunction (SD), there is no sufficient data on the relationship between serum Ucn-2 and diastolic dysfunction (DD), or coronary artery disease (CAD). We investigated serum Ucn-2 levels in SD, DD, and CAD. Methods: In this observational cross-sectional study, study population was enrolled among outpatients who underwent coronary angiography with the pre-diagnosis of CAD. By examining the echocardiography 86 subjects were selected to study after coronary angiography. The subjects distributed over three groups to investigate the relationship between serum Ucn-2 and SD according to their ejection fraction (EF): subjects with moderate to severe SD (Group A, EF=33.6%), subjects with mild to moderate SD (Group B, EF=46.1%), and those without SD (Group C, EF=64.5%). Apart from these groups, the serum Ucn-2 levels were compared between subjects with and without DD (EF≥45%), and also compared between subjects with and without CAD (EF≥55%). Statistical analyses were performed using one-way ANOVA, Kruskal-Wallis, Chisquare, Mann-Whitney U, Spearman correlation and multiple regression analyses tests. Results: Serum Ucn-2 levels were decreased in Group A and were increased in Group B compared to Group C (9.4±3.4, 12.8±3.6 vs. 10.4±3.9 pg/ mL, respectively, p=0.003). Unlike SD; there was no significant difference in serum Ucn-2 levels between subjects with and without DD (11.4±4.1 vs 11.7±3.9 pg/mL, p=0.8) or CAD (10.7±4.7 vs 10.2±3.2 pg/mL, p=0.7). Conclusion: Ucn-2 is elevated in mild to moderate SD. But, DD (impaired relaxation pattern), or CAD (without myocardial infarction) seems to have no effect on Ucn-2 hormone levels. (Anadolu Kardiyol Derg 2012; 12: 115-20) Key words: Urocortin 2, left ventricular systolic and diastolic dysfunction, coronary artery disease, regression analysis 115 ÖZET Amaç: Urocortin (Ucn) hormonları kardiyovasküler sistemde önemli rol oynamaktadır. Sistolik işlev bozukluğu (SD) dışında, diyastolik işlev bozukluğu (DD) veya koroner arter hastalığının (KAH) serum Ucn-2 ile ilişkisine dair yeterli veri bulunmamaktadır. Bu çalışmamızda SD, DD ve KAH'da serum Ucn-2 düzeyini araştırdık. Yöntemler: Bir gözlemsel enine-kesitli olan bu çalışmanın popülasyonu KAH ön tanısı ile koroner anjiyografi işlemine alınan bireyler arasından belirlendi. Koroner anjiyografi sonrası ekokardiyografi yapılarak 86 kişi seçildi. Ucn-2 ile SD arasındaki ilişkiyi araştırmak için ejeksiyon fraksiyonu (EF) farklı üç grup oluşturuldu: orta-ileri düzey SD olanlar (Grup A, EF=%33.6), hafif-orta SD olanlar (Grup B, EF=%46

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“…While urocortin reduces serum TNF-α and IL-1B levels, it increases IL-6 secretion. Urocortin is a potent mediator in mast cell degranulation and increases vascular permeability [9].…”

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Evaluation of the Ki-67 Proliferation Index and Urocortin Expression in Women with Ovarian Endometriomas

Yalçın¹,

Ocal²,

Yalçın³

et al. 2017

Eurasian J Med

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Objective: The reasons why endometriosis is more aggressive and invasive in some patients are unknown. Despite the importance of population-based clinically defined risk factors in the prediction of recurrence, biochemical markers obtained from the patient are more valuable for prediction on an individual basis. Therefore, the discovery of significant potential biomarkers could be useful to clinicians for shedding light on the pathogenesis of endometriosis and in the monitoring recurrence. Materials and Methods:This study included 50 patients who underwent surgery for ovarian cysts that were diagnosed as endometrioma. The age of the patients, stage of the endometriosis, diameter and localization of endometriomas, type of surgery, and pre-and postoperative cancer antigen 125 (CA125) levels were compared between patients with and without recurrence. The archived pathology slides were stained with Ki-67 and anti-urocortin antibodies for reevaluation. By comparing the pathology parameters of the patients with and without recurrence, the association between these parameters and recurrence was investigated.Results: The median Ki-67 proliferation index of the patients with recurrence (7.5±6.5) was statistically significant compared with that of the patients without recurrence (1±4) (p=0.003). The urocortin epithelial staining intensity and percentage were not found to be statistically significant in comparison. A statistically significant difference was determined between postoperative CA125 median levels of patients without recurrence (10±17.6) and those of patients with recurrence (29.9±18.1) (p=0.003). Conclusion:The Ki-67 proliferation index may be useful for predicting prognosis and recurrence risk.Keywords: Endometriosis, Ki-67 proliferation index, urocortin ÖZ Amaç: Endometriozisin bazı hastalarda neden daha agresif ve invaziv olduğunun nedenleri bilinmemektedir. Klinik olarak belirlenen risk faktörleri populasyon bazında rekürrens prediksiyonunda değerli olmasına rağmen kişi bazında prediksiyonda hastadan elde edilen biyokimyasal markerlar daha değerlidir. Bu nedenle, rekürrens açısından anlamlı potansiyel biyomarkerların keşfi endomeriozis patogenezine ışık tutabileceği gibi rekürrens takibinde klinisyenlere yardımcı bir parametre olarak kullanılabilir.Gereç ve Yöntem: Çalışmamıza over kisti nedeniyle cerrahi geçiren ve patolojik inceleme sonucunda endometrioma tanısı konmuş 50 hasta dahil edildi. Olguların yaş, endometriozis evresi, endometrioma çapı ve lokalizasyonu, cerrahi tipi, preoperatif ve postoperatif CA 125 düzeyleri kaydedildi. Olguların arşiv patoloji preparatları Ki 67 ve anti-urocortin antikor ile boyandı. Patolojik parametreler nüks olan olgular ile olmayanlarda kıyaslanarak bu parametrelerin rekürrens ile ilişkisi araştırıldı.Bulgular: Nüks olan olguların Ki67 İndeks medyanı (7,5±6,5) nüks olmayan olguların Ki67 İndeks medyan değerinden (1±4) daha büyük olup, istatistiksel olarak anlamlıydı (p=0,003). Olguların nüks olma durumu ile ürocortin epitel boyanma yoğunluğu ve yüzdesine göre da...

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Corticosteroid-independent inhibition of tumor necrosis factor production by the neuropeptide urocortin

Cited by 51 publications

References 30 publications

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

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

Relationship of urocortin-2 with systolic and diastolic functions and coronary artery disease: an observational study

Evaluation of the Ki-67 Proliferation Index and Urocortin Expression in Women with Ovarian Endometriomas

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