Corticotropin-releasing factor family and its receptors: pro-inflammatory or anti-inflammatory targets in the periphery?

Zhu, Huayuan; Wang, Juejin; Li, Jianyong; Li, Shengnan

doi:10.1007/s00011-011-0329-2

Cited by 20 publications

(14 citation statements)

References 63 publications

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“…In addition to its effects on Bcl-2 and mitochondrial apoptosis, p38 also affects a wide spectrum of other cell signaling molecules including mTOR [10,[35][36][37] and inflammatory pathways [10,36,38]. Our data suggest that mTOR does not play a role in UCN2-induced protection as UCN2 did not affect mTOR expression and phosphorylation.…”

Section: Discussionmentioning

confidence: 70%

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Urocortin-2 suppression of p38-MAPK signaling as an additional mechanism for ischemic cardioprotection

et al. 2014

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Urocortin-2 (UCN2) is cardioprotective in ischemia/reperfusion injury (I/R) through short-lived activation of ERK1/2. Key factors involved in I/R, e.g. apoptosis, mitochondrial damage, p38 kinase, and Bcl-2 family, have not been well-investigated in UCN2-induced cardioprotection. We assessed the role of p38-MAPK in anti-apoptotic Bcl-2 signaling and mitochondrial stabilization as a putative mechanisms in UCN2-induced cardioprotection. Isolated hearts from adult Sprague-Dawley rats and cultured H9c2 cells were subjected to I/R protocols with or without 10 nM UCN2 treatment. The effect of a specific p38 inhibitor SB202190 was tested in H9c2 cells. Cardiac function, LDH release, and mitochondrial membrane potential (MMP) were used to assess the degree of myocardial injury in hearts and H9c2 cells. Post-perfusion, hearts were collected for Western blot analyses or mitochondria/cytosol isolation to analyze p38 activation and Bcl-2 family members. UCN2 treatment improved rate-pressure product (58 ± 5 vs. 31 ± 4 % of Baseline; P < 0.05) and decreased LDH release (20 ± 9 vs. 90 ± 40 mU/ml LDH, P < 0.01) at the end of 60 min reperfusion. UCN2 reduced phospho-p38 levels and Bax activation. UCN2 increased the expression of Bcl-2 and inhibited the accumulation of p-Bim. With additional experiments, it was confirmed that UCN2 increases the phosphorylation of ERK1/2 in the early phase of UCN2 treatment and increases the overshot recovery of ERK1/2 phosphorylation during reperfusion. UCN2 and SB202190 partially prevented the loss of MMP induced by I/R. However, combined treatment with UCN2 and SB202190 did not provide additive benefit. UCN2 is cardioprotective in I/R in association with reduced phosphorylation of p38 together with the increased ERK1/2 activation and increased Bcl-2 family member pro-survival signaling. These changes may stabilize cardiac mitochondria, similar to p38 inhibitors, as part of a pro-survival mechanism during I/R.

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Section: Discussionmentioning

confidence: 70%

“…Our data suggest that mTOR does not play a role in UCN2-induced protection as UCN2 did not affect mTOR expression and phosphorylation. It is still controversial whether CRF2-Receptor mediates pro-inflammatory or anti-inflammatory reactions [36]. At an extremely high concentration of 100 nM, UCN2 induces myocytes to release IL-6 [39].…”

Section: Discussionmentioning

confidence: 99%

Urocortin-2 suppression of p38-MAPK signaling as an additional mechanism for ischemic cardioprotection

et al. 2014

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“…In the CNS, CRH modulates the synthesis and release of adrenocorticotropic hormone, which in turn stimulates the production of glucocorticoids, exerting anti-inflammatory effects (Bateman et al 1989). However, recent findings have revealed that large quantities of peripheral CRH-related peptides function as proinflammatory factors (Webster et al 1998, Elenkov & Chrousos 1999, Zhu et al 2011. Our previous data also demonstrated that UCN1 could increase lipopolysaccharide (LPS)-induced endothelial permeability by disrupting the VE-cadherin-b-catenin complex (Wan et al 2013).…”

Section: Introductionmentioning

confidence: 98%

The role of corticotropin-releasing hormone receptor 1 in the development of colitis-associated cancer in mouse model

Liu

Fang

Yuan

et al. 2014

Endocrine-Related Cancer

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Patients with ulcerative colitis are at a very high risk of developing colorectal cancer. Corticotrophin-releasing hormone (CRH) family peptides and their receptors (CRHRs) are found to modulate inflammation and tumor cell growth. However, the role of CRH family peptides and their receptors in the inflammation-related colon cancer is still unknown. The aim of this study was to investigate the functions of CRHR1 signaling on the development of colitis-associated cancer (CAC). Crhr1-deficient (Crhr1 K/K ) mice were used to explore the role of CRHR1 in the development of azoxymethane (AOM) and dextran sodium sulfate (DSS)-induced CAC. WT (Crhr1 C/C ) littermates were set as control. We found that the expression of CRHR1 and its endogenous ligands: urocortin and CRH were enhanced in the colon of Crhr1 C/C mice during treatment with AOM and DSS. Tumorigenesis was significantly reduced in Crhr1 K/K mice, determined by analysis of survival rate (increased by 20%), weight loss (decreased by 10%), tumor formation (decreased by 60% in tumor number), histological scores (decreased by 58%), and cytokine production. During early CAC tumorigenesis, Crhr1 K/K mice exhibited much less tumorigenesis, accompanied by lower inflammatory response, including decreased IL1b, IL6 and TNFa expression and macrophage infiltration and increased IL10 expression. Moreover, Crhr1 K/K mice displayed a reduced activation of NFkB and STAT3 phosphorylation with decreased proliferating and enhanced apoptotic cells in the colon. In conclusion, CRHR1 has a proinflammatory and therefore a protumorigenesis effect in terms of CAC, which may be helpful to develop new therapeutic approaches for inflammation and cancer prevention and treatment.

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“…Its ability to influence immune function is commonly associated with the release of adrenal corticotropic hormone (ACTH) from the adrenal glands, resulting in cortisol release that in turn translates into nonspecific immune suppression (Rodgers and Klugman 2011). Alternatively, CRH is also secreted in peripheral tissues (e.g., synovial tissue, gastrointestinal tract, placenta), where it is believed to modulate cellular immune and inflammatory responses through preferences in CRH receptors 1 and 2 activity (Peracoli et al 2011;Zhu et al 2011;Liu et al 2014). To date, few studies have defined the role of CRH in the regulation of pulmonary cellular immune and inflammatory responses (O'Kane et al 2006).…”

Section: Discussionmentioning

confidence: 99%

Corticotropin-releasing hormone improves survival in pneumococcal pneumonia by reducing pulmonary inflammation

Burnley

Jones

2017

Physiol Rep

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The use of glucocorticoids to reduce inflammatory responses is largely based on the knowledge of the physiological action of the endogenous glucocorticoid, cortisol. Corticotropin‐releasing hormone (CRH) is a neuropeptide released from the hypothalamic–pituitary–adrenal axis of the central nervous system. This hormone serves as an important mediator of adaptive physiological responses to stress. In addition to its role in inducing downstream cortisol release that in turn regulates immune suppression, CRH has also been found to mediate inflammatory responses in peripheral tissues. Streptococcus pneumoniae is a microorganism commonly present among the commensal microflora along the upper respiratory tract. Transmission of disease stems from the resident asymptomatic pneumococcus along the nasal passages. Glucocorticoids are central mediators of immune suppression and are the primary adjuvant pharmacological treatment used to reduce inflammatory responses in patients with severe bacterial pneumonia. However, controversy exists in the effectiveness of glucocorticoid treatment in reducing mortality rates during S. pneumoniae infection. In this study, we compared the effect of the currently utilized pharmacologic glucocorticoid dexamethasone with CRH. Our results demonstrated that intranasal administration of CRH increases survival associated with a decrease in inflammatory cellular immune responses compared to dexamethasone independent of neutrophils. Thus, providing evidence of its use in the management of immune and inflammatory responses brought on by severe pneumococcal infection that could reduce mortality risks.

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Corticotropin-releasing factor family and its receptors: pro-inflammatory or anti-inflammatory targets in the periphery?

Cited by 20 publications

References 63 publications

Urocortin-2 suppression of p38-MAPK signaling as an additional mechanism for ischemic cardioprotection

Urocortin-2 suppression of p38-MAPK signaling as an additional mechanism for ischemic cardioprotection

The role of corticotropin-releasing hormone receptor 1 in the development of colitis-associated cancer in mouse model

Corticotropin-releasing hormone improves survival in pneumococcal pneumonia by reducing pulmonary inflammation

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