Ghrelin inhibits LPS-induced release of IL-6 from mouse dopaminergic neurones

Beynon, Amy L.; Brown, M. Rowan; Wright, R. P.; Rees, Mark I.; Sheldon, I. Martin; Davies, J. S.

doi:10.1186/1742-2094-10-40

Cited by 47 publications

(38 citation statements)

References 25 publications

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“…Ghrelin can cross the blood-brain barrier and act bidirectionally in the periphery and in the brain. In addition to its well-known role as a regulator of energy balance and food intake, Ghrelin may be involved in several brain mechanisms (Méquinion et al, 2013), many of those are altered in mood disorders as circadian rhythms (Kluge et al, 2013) and neuroinflammation (Miyake and Yamamura, 2009;Beynon et al, 2013). All these evidences indicated that an imbalance in Glucagon, GLP-1, GIP and Ghrelin levels might play a role in the pathogenesis of BD and in the mechanism causing the comorbidity between mood and metabolic disorders (Czepielewski et al, 2013).…”

Section: Discussionmentioning

confidence: 99%

Glucose metabolism alterations in patients with bipolar disorder

Rosso

Cattaneo

Zanardini

et al. 2015

Journal of Affective Disorders

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Patients with bipolar disorder (BD) are more frequently affected by metabolic syndrome (MetS) than the general population, but the neurobiological correlates underlying such association are still not clarified and few studies in BD have evaluated the role of regulators of lipid and glucose metabolism. The present study was aimed to investigate putative alterations in markers linked to metabolic dysfunctions as C-peptide, Ghrelin, GIP, GLP-1, Glucagon, Insulin, Leptin, PAI-1 (total), Resistin and Visfatin in a sample of BD patients compared to controls. Furthermore, associations between changes of metabolic markers and relevant clinical features, such as severity of symptomatology, number and type of past mood episodes, drug treatments and presence/absence of metabolic alterations (MetS, diabetes and cardiovascular disease) were analyzed. A total of 57 patients with BD and 49 healthy controls were recruited. The main results showed lower serum levels of Glucagon, GLP-1, Ghrelin, and higher levels of GIP in BD patients as compared to controls (p = 0.018 for Ghrelin; p < 0.0001 for Glucagon; p < 0.0001 for GLP-1; p < 0.0001 for GIP). Further, Glucagon and GLP-1 levels were significantly associated with the number of past mood episodes. These findings support the hypothesis that alterations in Glucagon, GLP-1, GIP and Ghrelin might be involved in BD pathogenesis and might represent useful biomarkers for the development of preventive and personalized therapies in this disorder.

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Section: Discussionmentioning

confidence: 99%

Glucose metabolism alterations in patients with bipolar disorder

Rosso

Cattaneo

Zanardini

et al. 2015

Journal of Affective Disorders

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Section: Discussionmentioning

confidence: 99%

“…It is unknown if TLR4 agonists activate AKT or GSK3 signaling in SN4741 cells, as they do in myeloid cells [44,45]. However, LPS induces IL-6 production and NF-κB activation in the SN4741 cells [46]. Recent studies showed that monocytes, macrophages, DCs, and microglia when preexposed to recombinant Wnt3a and Wnt5a displayed phenotypic changes upon subsequent TLR stimulation, including impaired proinflammatory cytokine expression, elevated IL-10 production, and NF-κB p50-homodimers [21,[24][25][26].…”

mentioning

confidence: 99%

Recombinant Wnt3a and Wnt5a elicit macrophage cytokine production and tolerization to microbial stimulation via Toll‐like receptor 4

Nguyen

Irvine

et al. 2014

Eur J Immunol

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An increasing number of studies address the roles of Wnt proteins in shaping leukocyte functions. Recombinant Wnt3a and Wnt5a, prototypical activators of β-Catenindependent and -independent Wnt signaling, respectively, are widely used to investigate the effects of Wnt proteins on myeloid cell functions. Recent reports describe both proinflammatory and immunemodulatory effects of Wnt3a and Wnt5a on macrophages, DCs, and microglia. The underlying molecular mechanisms for this divergence are unclear. We show here that recombinant Wnt3a-and Wnt5a-induced cytokine production from murine C57BL/6 macrophages was dependent on TLR4 and inhibited by Polymyxin B. Similarly, impairment of TLR-induced cytokine production upon preexposure to Wnt proteins was TLR4 dependent. The extent of Wnt3a-and Wnt5a-induced inflammatory gene expression greatly varied between Wnt protein lots. We conclude that cytokine responses and TLR tolerization induced by recombinant Wnt proteins are likely explained by contaminating TLR4 agonists, although we cannot fully exclude that Wnt proteins have an intrinsic capacity to signal via TLR4. This study emphasizes the need for careful, independent verification of Wnt-mediated cellular responses. Keywords: Cytokines r Macrophages r TLR r Wnt proteinsAdditional supporting information may be found in the online version of this article at the publisher's web-site IntroductionWnt proteins are secreted regulators of cellular proliferation and differentiation. The 19 mammalian homologues have distinct expression patterns in embryonic and adult tissues and their Correspondence: Dr. Antje Blumenthal e-mail: a.blumenthal@uq.edu.au functions in embryogenesis and tissue homeostasis have been widely studied [1]. Recent associations of increased Wnt expression with bacterial infections and chronic inflammation in patients and model systems have created considerable interest in immunerelated Wnt functions. Elevated Wnt expression has been reported * These authors contributed equally to this work.C 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim www.eji-journal.eu Eur. J. Immunol. 2014. 44: 1480-1490 Innate immunity 1481 during infections with mycobacteria, Gram-negative and Grampositive bacteria [2][3][4][5][6], and chronic inflammation in rheumatoid arthritis, atherosclerosis, obesity, and psoriasis [7][8][9][10][11][12]. Inflammatory cytokines and chemokines are common drivers of these diverse pathologies. Endogenous Wnt proteins, in particular Wnt5a, have been shown to induce and enhance the production of inflammatory cytokines (e.g. IL-12 and IL-6) and chemokines (e.g. CCL2 and CCL5) by macrophages and other cell types [2,6,11,13,14]. Wnt proteins, such as Wnt5a, which signal via β-Catenin-independent pathways, including Ca 2+ mobilization, NF-κB, and MAP kinase activation, have been proposed to amplify local inflammation [15,16]. In contrast, Wnt proteins that stabilize the transcriptional co-activator β-Catenin, such as Wnt3a, are thought to have anti-inflammatory roles, e.g. suppression of cytokine expressi...

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“…30 Ghrelin, vagus nerve stimulation, glutamine, propofol, and Nrf2 use different mechanisms to regulate TNF-a. For example, ghrelin binds the growth hormone secretagogue receptor (GHS-R) on immune cells and inhibits PAMPinduced release of TNF-a, 31 and vagus nerve stimulation promotes the release of acetylcholine (ACh) by efferent vagus nerves to inhibit the production of TNFa by acetylcholine receptor (AChR)-expressing immune cells. 32 TNF-a expression in mammals is induced by Toll-like receptor (TLR) signaling pathways in macrophages and other cytokine-producing cells that are part of the defense mechanism provided by the innate immune response.…”

Section: Tbi Activates a Feedback Loop That Enhances Intestinal Permementioning

confidence: 99%