scholarly journals Vagus nerve controls resolution and pro-resolving mediators of inflammation

2014 ◽  
Vol 211 (6) ◽  
pp. 1037-1048 ◽  
Author(s):  
Valbona Mirakaj ◽  
Jesmond Dalli ◽  
Tiago Granja ◽  
Peter Rosenberger ◽  
Charles N. Serhan

Resolution of inflammation is now recognized as a biosynthetically active process involving pro-resolving mediators. Here, we show in zymosan-initiated peritoneal inflammation that the vagus nerve regulates local expression of netrin-1, an axonal guidance molecule that activates resolution, and that vagotomy reduced local pro-resolving mediators, thereby delaying resolution. In netrin-1+/− mice, resolvin D1 (RvD1) was less effective in reducing neutrophil influx promoting resolution of peritonitis compared with Ntn1+/+. Netrin-1 shortened the resolution interval, decreasing exudate neutrophils, reducing proinflammatory mediators, and stimulating the production of resolvins, protectins, and lipoxins. Human monocytes incubated with netrin-1 produced proresolving mediators, including resolvins and lipoxins. Netrin-1 and RvD1 displayed bidirectional activation in that they stimulated each other’s expression and enhanced efferocytosis. These results indicate that the vagus nerve regulates both netrin-1 and pro-resolving lipid mediators, which act in a bidirectional fashion to stimulate resolution, and provide evidence for a novel mechanism for local neuronal control of resolution.

2020 ◽  
Vol 20 (1) ◽  
pp. 51-55
Author(s):  
Bo Sun ◽  
Tian Su ◽  
Zhibin Meng ◽  
Songjie Tang

Postmenopausal and ovariectomy-induced osteoporosis is the most common bone disorder. While pharmacotherapy has been valuable in the management of osteoporosis, it has been associated with undesired side effects. Plant bioactives with minimal side effects have been seen as adjunct to classical therapy. Herein, we have evaluated the protective effect of anhuienoside C (AC) in a rat model of ovariectomy-induced osteoporosis. The treatment of osteoporotic rats with AC caused dose-dependent favorable changes in biochemical markers of bone formation and metabolism (osteocalcin, C-telopeptide of type 1 collagen, and procollagen type 1 N-terminal propeptide), enhanced bone mineral density, and decrease in proinflammatory mediators of inflammation and RANKL/Wnt pathway proteins. Furthermore, histopathologic changes in the tibia support beneficial effects of AC. In conclusion, our result reveals that treatment with AC shows beneficial effect against ovariectomy-induced osteoporosis by regulating the RANKL/Wnt pathway.


Author(s):  
Katarzyna Grzesiak ◽  
Aleksandra Rył ◽  
Ewa Stachowska ◽  
Marcin Słojewski ◽  
Iwona Rotter ◽  
...  

Background: The purpose of our investigation was to analyze the relationship between the serum levels of inflammatory mediators (HETE, HODE) and the levels of selected metabolic and hormonal parameters in patients with benign prostatic hyperplasia (BPH) with regard to concomitant metabolic syndrome (MetS). Methods: The study involved 151 men with BPH. Blood samples were taken for laboratory analysis of the serum levels of metabolic and hormonal parameters. Gas chromatography was performed using an Agilent Technologies 7890A GC System. Results: We found that waist circumference was the only parameter related to the levels of fatty acids, namely: 13(S)-HODE, 9(S)-HODE, 15(S)-HETE, 12(S)-HETE, and 5-HETE. In the patients with BPH and MetS, triglycerides correlated with 9(S)-HODE, 15(S)-HETE, 12(S)-HETE, and 5-HETE, which was not observed in the patients without MetS. Similarly, total cholesterol correlated with 9(S)-HODE, and 15(S)-HETE in the patients with BPH and MetS, but not in those without MetS. In the group of BPH patients with MetS, total testosterone positively correlated with 13(S)-HODE, and free testosterone with 9(S)-HODE. Conclusions: Based on this study, it can be concluded that lipid mediators of inflammation can influence the levels of biochemical and hormonal parameters, depending on the presence of MetS in BPH patients.


2020 ◽  
Vol 21 (16) ◽  
pp. 5783 ◽  
Author(s):  
Keishi Miyazawa ◽  
Hisanori Fukunaga ◽  
Yasuko Tatewaki ◽  
Yumi Takano ◽  
Shuzo Yamamoto ◽  
...  

Alzheimer’s disease (AD) is a common neurodegenerative disease and a major contributor to progressive cognitive impairment in an aging society. As the pathophysiology of AD involves chronic neuroinflammation, the resolution of inflammation and the group of lipid mediators that actively regulate it—i.e., specialized pro-resolving lipid mediators (SPMs)—attracted attention in recent years as therapeutic targets. This review focuses on the following three specific SPMs and summarizes their relationships to AD, as they were shown to effectively address and reduce the risk of AD-related neuroinflammation: maresin 1 (MaR1), resolvin D1 (RvD1), and neuroprotectin D1 (NPD1). These three SPMs are metabolites of docosahexaenoic acid (DHA), which is contained in fish oils and is thus easily available to the public. They are expected to become incorporated into promising avenues for preventing and treating AD in the future.


2004 ◽  
Vol 72 (12) ◽  
pp. 7247-7256 ◽  
Author(s):  
Samithamby Jeyaseelan ◽  
Hong Wei Chu ◽  
Scott K. Young ◽  
G. Scott Worthen

ABSTRACT Mortality associated with acute lung injury (ALI) induced by lipopolysaccharide (LPS) remains high in humans, warranting improved treatment and prevention strategies. ALI is characterized by the expression of proinflammatory mediators and extensive neutrophil influx into the lung, followed by severe lung damage. Understanding the pathogenesis of LPS-induced ALI is a prerequisite for designing better therapeutic strategies. In the present study, we used microarrays to gain a global view of the transcriptional responses of the lung to LPS in a mouse model of ALI that mimics ALI in humans. A total of 71 inflammation-associated genes were up-regulated in LPS-treated lungs, including a chemokine, LPS-induced CXC chemokine (LIX), whose role in the induction of ALI is unknown. Most of the inflammatory genes peaked at 2 h post-LPS treatment. Real-time reverse transcription-PCR confirmed the LPS-induced up-regulation of selected genes identified by microarray analysis, including LIX. The up-regulation of LIX, tumor necrosis factor alpha, and macrophage inflammatory protein 2 was confirmed at the protein level by enzyme-linked immunosorbent assays. To determine the role of LIX in the induction of ALI, we used both exogenous LIX and a LIX blocking antibody. Exogenous LIX alone elicited a neutrophil influx in the lungs, and the anti-LIX antibody attenuated the LPS-induced neutrophil accumulation in the lungs. Taken together, the results of our study demonstrate for the first time the temporal expression of inflammatory genes during LPS-induced ALI and suggest that early therapeutic intervention is crucial to attenuate lung damage. Moreover, we identified a role for LIX in the induction of ALI, and therefore LIX may serve as a novel therapeutic target for the minimization of ALI.


2018 ◽  
Vol 86 (4) ◽  
Author(s):  
Romain A. Colas ◽  
Anthony W. Ashton ◽  
Shankar Mukherjee ◽  
Jesmond Dalli ◽  
Oscar B. Akide-Ndunge ◽  
...  

ABSTRACT Trypanosoma cruzi is a protozoan parasite that causes Chagas disease (CD). CD is a persistent, lifelong infection affecting many organs, most notably the heart, where it may result in acute myocarditis and chronic cardiomyopathy. The pathological features include myocardial inflammation and fibrosis. In the Brazil strain-infected CD-1 mouse, which recapitulates many of the features of human infection, we found increased plasma levels of resolvin D1 (RvD1), a specialized proresolving mediator of inflammation, during both the acute and chronic phases of infection (>100 days postinfection) as determined by enzyme-linked immunosorbent assay (ELISA). Additionally, ELISA on lysates of trypomastigotes of both strains Tulahuen and Brazil revealed elevated levels of RvD1 compared with lysates of cultured epimastigotes of T. cruzi , tachyzoites of Toxoplasma gondii , trypomastigotes of Trypanosoma brucei , cultured L 6 E 9 myoblasts, and culture medium containing no cells. Lysates of T. cruzi -infected myoblasts also displayed increased levels of RvD1. Lipid mediator metabolomics confirmed that the trypomastigotes of T. cruzi produced RvD1, RvD5, and RvE2, which have been demonstrated to modulate the host response to bacterial infections. Plasma RvD1 levels may be both host and parasite derived. Since T. cruzi synthesizes specialized proresolving mediators of inflammation, as well as proinflammatory eicosanoids, such as thromboxane A 2 , one may speculate that by using these lipid mediators to modulate its microenvironment, the parasite is able to survive.


1990 ◽  
Vol 153 (1) ◽  
pp. 29-46
Author(s):  
B. Muller ◽  
B. Stahl ◽  
F. Bonhoeffer

In the retinotectal projection, nasal retinal axons project to posterior tectum, while temporal axons project to the anterior part of the tectum. In in vitro experiments, a similar specificity can be observed: the nasal and temporal retinal axons can be guided by tectal membrane components so that, for example, temporal retinal axons, when growing on a striped substratum consisting of anterior and posterior tectal membranes, express a very strong preference for the anterior stripes. This preference is not due to attractivity of anterior membranes but rather to avoidance of posterior material, although the pure posterior membranes are a very good substratum for growth of temporal axons. The repellent guidance molecule has been identified. Interestingly, besides guidance this molecule causes another reaction: when growing temporal axons are exposed to medium containing either posterior membranes or artificial lipid vesicles containing the repellent guidance molecule, the axonal growth cones collapse. As in guidance, there is a clear regional specificity: e.g. the repellent guidance molecule derived from posterior tectum induces collapse of temporal but not of nasal axons. Since the guiding and the collapse-inducing activity are expressed by one and the same glycoprotein molecule (Mr 33 × 10(3), linked to the membrane by phosphatidylinositol) and since another molecule has been identified by Keynes' group which also expresses both guiding and collapse-inducing activity, one might speculate that axonal guidance and axonal collapse have something in common. Models of axonal guidance will be discussed.


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