scholarly journals The Cholinergic Anti-Inflammatory Pathway as a Conceptual Framework to Treat Inflammation-Mediated Renal Injury

2019 ◽  
Vol 44 (4) ◽  
pp. 435-448 ◽  
Author(s):  
Jonas Jarczyk ◽  
Benito A. Yard ◽  
Simone Hoeger
Keyword(s):  
Vagus Nerve ◽  
Inflammatory Responses ◽  
Current Knowledge ◽  
Kidney Injury ◽  
Organ Injury ◽  
Inflammatory Pathway ◽  
Inflammatory Conditions ◽  
Promising Strategy ◽  
Anti Inflammatory ◽  
The Brain

Background: The cholinergic anti-inflammatory pathway, positioned at the interface of the nervous and immune systems, is the efferent limb of the “inflammatory reflex” which mainly signals through the vagus nerve. As such, the brain can modulate peripheral inflammatory responses by the activation of vagal efferent fibers. Importantly, immune cells in the spleen express most cholinergic system components such as acetylcholine (ACh), choline acetyltransferase, acetylcholinesterase, and both muscarinic and nicotinic ACh receptors, making communication between both systems possible. In general, this communication down-regulates the inflammation, achieved through different mechanisms and depending on the cells involved. Summary: With the awareness that the cholinergic anti-inflammatory pathway serves to prevent or limit inflammation in peripheral organs, vagus nerve stimulation has become a promising strategy in the treatment of several inflammatory conditions. Both pharmacological and non-pharmacological methods have been used in many studies to limit organ injury as a consequence of inflammation. Key Messages: In this review, we will highlight our current knowledge of the cholinergic anti-inflammatory pathway, with emphasis on its potential clinical use in the treatment of inflammation-triggered kidney injury.

Controlling inflammation: the cholinergic anti-inflammatory pathway

2006 ◽  
Vol 34 (6) ◽  
pp. 1037-1040 ◽  
Author(s):  
V.A. Pavlov ◽  
K.J. Tracey
Keyword(s):  
Vagus Nerve ◽  
Nicotinic Receptor ◽  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Experimental Models ◽  
Innate Immune Responses ◽  
Receptor Ligands ◽  
Inflammatory Pathway ◽  
Anti Inflammatory ◽  
Inflammatory Signalling

Innate immune responses and inflammation are regulated in part by neural mechanisms. In the present paper, we summarize experimental evidence that reveals that innate immunity and inflammation are controlled by the vagus nerve, previously known as a regulator of other vital physiological functions. Activation of vagus nerve cholinergic signalling inhibits TNF (tumour necrosis factor) and other pro-inflammatory cytokine overproduction through ‘immune’ α7 nicotinic receptor-mediated mechanisms. This efferent vagus nerve-based ‘cholinergic anti-inflammatory pathway’ has been elucidated as a critical regulator of inflammation in several experimental models of diseases. Our recent observations have shown that activation of central (brain) cholinergic transmission by selective muscarinic receptor ligands results in lower systemic TNF levels in rodents and indicate that the efferent vagus nerve may provide a functional brain-to-immune connection. Thus central cholinergic signalling is implicated in the activation of the cholinergic anti-inflammatory pathway. Electrical vagus nerve stimulation is clinically approved for the treatment of epilepsy and depression and current knowledge suggests that it could be utilized to control inflammation. Advances in understanding the receptor and molecular mechanisms of cholinergic anti-inflammatory signalling indicate that selective α7 nicotinic receptor agonists and centrally acting cholinergic enhancers can be used in the treatment of pathological conditions characterized by cytokine overproduction.

scholarly journals Transcutaneous Auricular Vagus Nerve Stimulation Protects Endotoxemic Rat from Lipopolysaccharide-Induced Inflammation

2012 ◽  
Vol 2012 ◽  
pp. 1-10 ◽  
Author(s):  
Yu Xue Zhao ◽  
Wei He ◽  
Xiang Hong Jing ◽  
Jun Ling Liu ◽  
Pei Jing Rong ◽  
...  
Keyword(s):  
Vagus Nerve ◽  
Proinflammatory Cytokines ◽  
Nerve Stimulation ◽  
Vagus Nerve Stimulation ◽  
Inflammatory Responses ◽  
Interleukin 1 ◽  
Nf Kappa B ◽  
Necrosis Factor Alpha ◽  
Inflammatory Pathway ◽  
Anti Inflammatory

Background. Transcutaneous auricular vagus nerve stimulation (ta-VNS) could evoke parasympathetic activities via activating the brainstem autonomic nuclei, similar to the effects that are produced after vagus nerve stimulation (VNS). VNS modulates immune function through activating the cholinergic anti-inflammatory pathway.Methods. VNS, ta-VNS, or transcutaneous electrical acupoint stimulation (TEAS) on ST36 was performed to modulate the inflammatory response. The concentration of serum proinflammatory cytokines and tissue NF-kappa B p65 (NF-κB p65) were detected in endotoxaemia affected anesthetized rats.Results. Similar to the effect of VNS, ta-VNS suppressed the serum proinflammatory cytokines levels, such as tumour necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), and interleukin-6 (IL-6) as well as NF-kappa B p65 expressions of lung tissues. ST36 stimulation also decreases LPS-induced high TNF-αlevel and NF-κB signal, but it did not restrain proinflammatory cytokine IL-1βand IL-6. Neither ta-VNS nor ST36 stimulation could suppress LPS-induced TNF-αand NF-κB after vagotomy or withα7nAChR antagonist injection.Conclusions. The present paper demonstrated that ta-VNS could be utilized to suppress LPS-induced inflammatory responses viaα7nAChR-mediated cholinergic anti-inflammatory pathway.

scholarly journals Vagal-Immune Interactions Involved in Cholinergic Anti-Inflammatory Pathway

2017 ◽  
pp. S139-S145 ◽  
Author(s):  
I. ZILA ◽  
D. MOKRA ◽  
J. KOPINCOVA ◽  
M. KOLOMAZNIK ◽  
M. JAVORKA ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Vagus Nerve ◽  
Current Knowledge ◽  
Nervous Activity ◽  
Treatment Strategies ◽  
Therapeutic Effects ◽  
Vagal Activity ◽  
Inflammatory Pathway ◽  
Autonomic Nervous ◽  
Anti Inflammatory

Inflammation and other immune responses are involved in the variety of diseases and disorders. The acute response to endotoxemia includes activation of innate immune mechanisms as well as changes in autonomic nervous activity. The autonomic nervous system and the inflammatory response are intimately linked and sympathetic and vagal nerves are thought to have anti-inflammation functions. The basic functional circuit between vagus nerve and inflammatory response was identified and the neuroimmunomodulation loop was called cholinergic anti-inflammatory pathway. Unique function of vagus nerve in the anti-inflammatory reflex arc was found in many experimental and pre-clinical studies. They brought evidence on the cholinergic signaling interacting with systemic and local inflammation, particularly suppressing immune cells function. Pharmacolo-gical/electrical modulation of vagal activity suppressed TNF-α and other proinflammatory cytokines production and had beneficial therapeutic effects. Many questions related to mapping, linking and targeting of vagal-immune interactions have been elucidated and brought understanding of its basic physiology and provided the initial support for development of Tracey´s inflammatory reflex. This review summarizes and critically assesses the current knowledge defining cholinergic anti-inflammatory pathway with main focus on studies employing an experimental approach and emphasizes the potential of modulation of vagally-mediated anti-inflammatory pathway in the treatment strategies.

scholarly journals The critical roles of histone deacetylase 3 in the pathogenesis of solid organ injury

2021 ◽  
Vol 12 (8) ◽  
Author(s):  
Li Ning ◽  
Xiong Rui ◽  
Wang Bo ◽  
Geng Qing
Keyword(s):  
Histone Deacetylase ◽  
Chromatin Remodeling ◽  
Current Knowledge ◽  
Organ Injury ◽  
Solid Organ ◽  
Solid Organ Injury ◽  
Histone Deacetylase 3 ◽  
Physiological Conditions ◽  
Inflammatory Conditions ◽  
Therapeutic Value

AbstractHistone deacetylase 3 (HDAC3) plays a crucial role in chromatin remodeling, which, in turn, regulates gene transcription. Hence, HDAC3 has been implicated in various diseases, including ischemic injury, fibrosis, neurodegeneration, infections, and inflammatory conditions. In addition, HDAC3 plays vital roles under physiological conditions by regulating circadian rhythms, metabolism, and development. In this review, we summarize the current knowledge of the physiological functions of HDAC3 and its role in organ injury. We also discuss the therapeutic value of HDAC3 in various diseases.

scholarly journals Selected Uterine Immune Events Associated With the Establishment of Pregnancy in the Dog

2021 ◽  
Vol 7 ◽  
Author(s):  
Miguel Tavares Pereira ◽  
Renata Nowaczyk ◽  
Rita Payan-Carreira ◽  
Sonia Miranda ◽  
Selim Aslan ◽  
...  
Keyword(s):  
Inflammatory Responses ◽  
Trophoblast Invasion ◽  
Tnf Receptors ◽  
Related Factors ◽  
Inflammatory Conditions ◽  
Inflammatory Signals ◽  
Anti Inflammatory ◽  
Uterine Glands ◽  
Post Implantation ◽  
Implantation Period

In the dog, implantation takes place at approximately 17 days of embryonal life and, while exposed to relatively high circulating progesterone concentrations, embryos presence is required for the formation of decidua. Furthermore, a balance between pro- and anti-inflammatory responses in conceptus-maternal communication is crucial for the onset of pregnancy. Strikingly, the understanding of such immune mechanisms in canine reproduction is still elusive. Here, canine uterine samples from pre-implantation (day 10–12, E+) and corresponding non-pregnant controls (E–), implantation (day 17, Imp) and post-implantation (day 18–25, Post-Imp) stages of pregnancy were used to investigate the expression and localization of several immune-related factors. The most important findings indicate increased availability of CD4, MHCII, NCR1, IDO1, AIF1, CD25, CCR7, and IL6 in response to embryo presence (E+), while FoxP3 and CCL3 were more abundant in E– samples. Implantation was characterized by upregulated levels of FoxP3, IL12a, ENG, and CDH1, whereas CD4, CCR7, IL8, and -10 were less represented. Following implantation, decreased transcript levels of TNFR1, MHCII, NCR1, TLR4, CD206, FoxP3, and IL12a were observed concomitantly with the highest expression of IL6 and IL1β. MHCII, CD86, CD206, CD163, TNFα, IDO1, and AIF1 were immunolocalized in macrophages, CD4 and Nkp46 in lymphocytes, and some signals of IDO1, AIF1, and TNF-receptors could also be identified in endothelial cells and/or uterine glands. Cumulatively, new insights regarding uterine immunity in the peri-implantation period are provided, with apparent moderated pro-inflammatory signals prevailing during pre-implantation, while implantation and early trophoblast invasion appear to be associated with immunomodulatory and rather anti-inflammatory conditions.

scholarly journals Wharton’s jelly-derived mesenchymal stem cells attenuate sepsis-induced organ injury partially via cholinergic anti-inflammatory pathway activation

2020 ◽  
Vol 318 (1) ◽  
pp. R135-R147 ◽  
Author(s):  
José Manuel Cóndor Capcha ◽  
Camila Eleutério Rodrigues ◽  
Roberto de Souza Moreira ◽  
Marcelo Duarte Silveira ◽  
Paulo Dourado ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Systemic Inflammation ◽  
Cecal Ligation ◽  
Wharton’S Jelly ◽  
Organ Injury ◽  
Experimental Sepsis ◽  
Inflammatory Pathway ◽  
Wharton's Jelly ◽  
Anti Inflammatory

Sepsis induces organ dysfunction due to overexpression of the inflammatory host response, resulting in cardiopulmonary and autonomic dysfunction, thus increasing the associated morbidity and mortality. Wharton’s jelly-derived mesenchymal stem cells (WJ-MSCs) express genes and secrete factors with anti-inflammatory properties, neurological and immunological protection, as well as improve survival in experimental sepsis. The cholinergic anti-inflammatory pathway (CAP) is mediated by α7-nicotinic acetylcholine receptors (α7nAChRs), which play an important role in the control of systemic inflammation. We hypothesized that WJ-MSCs attenuate sepsis-induced organ injury in the presence of an activated CAP pathway. To confirm our hypothesis, we evaluated the effects of WJ-MSCs as a treatment for cardiopulmonary injury and on neuroimmunomodulation. Male Wistar rats were randomly divided into four groups: control (sham-operated); cecal ligation and puncture (CLP) alone; CLP+WJ-MSCs (1 × 106 cells, at 6 h post-CLP); and CLP+methyllycaconitine (MLA)+WJ-MSCs (5 mg/kg body wt, at 5.5 h post-CLP, and 1 × 106 cells, at 6 h post-CLP, respectively). All experiments, including the assessment of echocardiographic parameters and heart rate variability, were performed 24 h after CLP. WJ-MSC treatment attenuated diastolic dysfunction and restored baroreflex sensitivity. WJ-MSCs also increased cardiac sympathetic and cardiovagal activity. WJ-MSCs reduced leukocyte infiltration and proinflammatory cytokines, effects that were abolished by administration of a selective α7nAChR antagonist (MLA). In addition, WJ-MSC treatment also diminished apoptosis in the lungs and spleen. In cardiac and splenic tissue, WJ-MSCs downregulated α7nAChR expression, as well as reduced the phospho-STAT3-to-total STAT3 ratio in the spleen. WJ-MSCs appear to protect against sepsis-induced organ injury by reducing systemic inflammation, at least in part, via a mechanism that is dependent on an activated CAP.

scholarly journals Antioxidative, Antiapoptotic, and Anti-Inflammatory Effects of Apamin in a Murine Model of Lipopolysaccharide-Induced Acute Kidney Injury

Molecules ◽  
2020 ◽  
Vol 25 (23) ◽  
pp. 5717 ◽  
Author(s):  
Jung-Yeon Kim ◽  
Jaechan Leem ◽  
Kwan-Kyu Park
Keyword(s):  
Oxidative Stress ◽  
Acute Kidney Injury ◽  
Immune Cell ◽  
Inflammatory Responses ◽  
Tissue Injury ◽  
Therapeutic Option ◽  
Nicotinamide Adenine Dinucleotide Phosphate ◽  
Kidney Injury ◽  
Heme Oxygenase 1 ◽  
Anti Inflammatory

Sepsis is the major cause of acute kidney injury (AKI) in severely ill patients, but only limited therapeutic options are available. During sepsis, lipopolysaccharide (LPS), an endotoxin derived from bacteria, activates signaling cascades involved in inflammatory responses and tissue injury. Apamin is a component of bee venom and has been shown to exert antioxidative, antiapoptotic, and anti-inflammatory activities. However, the effect of apamin on LPS-induced AKI has not been elucidated. Here, we show that apamin treatment significantly ameliorated renal dysfunction and histological injury, especially tubular injury, in LPS-injected mice. Apamin also suppressed LPS-induced oxidative stress through modulating the expression of nicotinamide adenine dinucleotide phosphate oxidase 4 and heme oxygenase-1. Moreover, tubular cell apoptosis with caspase-3 activation in LPS-injected mice was significantly attenuated by apamin. Apamin also inhibited cytokine production and immune cell accumulation, suppressed toll-like receptor 4 pathway, and downregulated vascular adhesion molecules. Taken together, these results suggest that apamin ameliorates LPS-induced renal injury through inhibiting oxidative stress, apoptosis of tubular epithelial cells, and inflammation. Apamin might be a potential therapeutic option for septic AKI.

Vagus nerve stimulation: from epilepsy to the cholinergic anti-inflammatory pathway

2013 ◽  
Vol 25 (3) ◽  
pp. 208-221 ◽  
Author(s):  
B. Bonaz ◽  
C. Picq ◽  
V. Sinniger ◽  
J. F. Mayol ◽  
D. Clarençon
Keyword(s):  
Vagus Nerve ◽  
Nerve Stimulation ◽  
Vagus Nerve Stimulation ◽  
Inflammatory Pathway ◽  
Anti Inflammatory

Protective effects of Lactobacillus reuteri and Bifidobacterium infantis in murine models for colitis do not involve the vagus nerve

2008 ◽  
Vol 295 (4) ◽  
pp. R1131-R1137 ◽  
Author(s):  
Hanneke van der Kleij ◽  
Caitlin O'Mahony ◽  
Fergus Shanahan ◽  
Liam O'Mahony ◽  
John Bienenstock
Keyword(s):  
Vagus Nerve ◽  
Lactobacillus Reuteri ◽  
Transfer Model ◽  
Cell Transfer ◽  
Protective Effects ◽  
Cytokine Levels ◽  
Anti Inflammatory ◽  
T Cell Transfer ◽  
The Brain

The vagus nerve is an important pathway signaling immune activation of the gastrointestinal tract to the brain. Probiotics are live organisms that may engage signaling pathways of the brain-gut axis to modulate inflammation. The protective effects of Lactobacillus reuteri ( LR) and Bifidobacterium infantis ( BI) during intestinal inflammation were studied after subdiaphragmatic vagotomy in acute dextran sulfate sodium (DSS) colitis in BALB/c mice and chronic colitis induced by transfer of CD4+ CD62L+ T lymphocytes from BALB/c into SCID mice. LR and BI (1 × 109) were given daily. Clinical score, myeloperoxidase (MPO) levels, and in vivo and in vitro secreted inflammatory cytokine levels were found to be more severe in mice that were vagotomized compared with sham-operated animals. LR in the acute DSS model was effective in decreasing the MPO and cytokine levels in the tissue in sham and vagotomized mice. BI had a strong downregulatory effect on secreted in vitro cytokine levels and had a greater anti-inflammatory effect in vagotomized- compared with sham-operated mice. Both LR and BI retained anti-inflammatory effects in vagotomized mice. In SCID mice, vagotomy did not enhance inflammation, but BI was more effective in vagotomized mice than shams. Taken together, the intact vagus has a protective role in acute DSS-induced colitis in mice but not in the chronic T cell transfer model of colitis. Furthermore, LR and BI do not seem to engage their protective effects via this cholinergic anti-inflammatory pathway, but the results interestingly show that, in the T cell, transfer model vagotomy had a biological effect, since it increased the effectiveness of the BI in downregulation of colonic inflammation.

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