Efferent Vagal Nerve Stimulation Attenuates Gut Barrier Injury After Burn: Modulation of Intestinal Occludin Expression

Costantini, Todd W.; Bansal, Vishal; Peterson, Carrie Y.; Loomis, William; Putnam, James G.; Rankin, Fermin; Wolf, Steven E.; Eliceiri, Brian P.; Baird, Andrew; Coimbra, Raúl

doi:10.1097/ta.0b013e3181dccea0

Cited by 73 publications

(76 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The Tracey laboratories, for example, established that efferent signaling of the vagus nerve acts exclusively via α7nAChR activation in the spleen to regulate systemic cytokine responses to infection in mice (15)(16)(17)(18)(19)(20). Similarly, Costantini and colleagues demonstrated the existence of a similar α7nAChR-dependent regulation of the local inflammatory response in tissues (21)(22)(23)(24)(25)(26)(27). With α7nAChR activation clearly essential to inflammation, not to mention vagus nerve responsiveness and leukocyte function (28,29), we reasoned that it was therefore critical to understand how a human-specific α7nAChR in human leukocytes might influence human leukocyte function, the regulation of its expression and the biological consequences of its expression.…”

Section: Introductionmentioning

confidence: 95%

A Human-Specific α7-Nicotinic Acetylcholine Receptor Gene in Human Leukocytes: Identification, Regulation and the Consequences of CHRFAM7A Expression

Costantini

Dang

Yurchyshyna

et al. 2015

Mol Med

Self Cite

View full text Add to dashboard Cite

The human genome contains a variant form of the α7-nicotinic acetylcholine receptor (α7nAChR) gene that is uniquely human. This CHRFAM7A gene arose during human speciation and recent data suggests that its expression alters ligand tropism of the normally homopentameric human α7-AChR ligand-gated cell surface ion channel that is found on the surface of many different cell types. To understand its possible significance in regulating inflammation in humans, we investigated its expression in normal human leukocytes and leukocyte cell lines, compared CHRFAM7A expression to that of the CHRNA7 gene, mapped its promoter and characterized the effects of stable CHRFAM7A overexpression. We report here that CHRFAM7A is highly expressed in human leukocytes but that the levels of both CHRFAM7A and CHRNA7 mRNAs were independent and varied widely. To this end, mapping of the CHRFAM7A promoter in its 5′-untranslated region (UTR) identified a unique 1-kb sequence that independently regulates CHRFAM7A gene expression. Because overexpression of CHRFAM7A in THP1 cells altered the cell phenotype and modified the expression of genes associated with focal adhesion (for example, FAK, P13K, Akt, rho, GEF, Elk1, CycD), leukocyte transepithelial migration (Nox, ITG, MMPs, PKC) and cancer (kit, kitL, ras, cFos cyclinD1, Frizzled and GPCR), we conclude that CHRFAM7A is biologically active. Most surprisingly however, stable CHRFAM7A overexpression in THP1 cells upregulated CHRNA7, which, in turn, led to increased binding of the specific α7nAChR ligand, bungarotoxin, on the THP1 cell surface. Taken together, these data confirm the close association between CHRFAM7A and CHRNA7 expression, establish a biological consequence to CHRFAM7A expression in human leukocytes and support the possibility that this human-specific gene might contribute to, and/or gauge, a human-specific response to inflammation.

show abstract

Section: Introductionmentioning

confidence: 95%

A Human-Specific α7-Nicotinic Acetylcholine Receptor Gene in Human Leukocytes: Identification, Regulation and the Consequences of CHRFAM7A Expression

Costantini

Dang

Yurchyshyna

et al. 2015

Mol Med

Self Cite

View full text Add to dashboard Cite

show abstract

“…Moreover, it is interesting that intestinal permeability have in several observations been found to be controlled by the vagus nerve 101,166 , further supporting participation of nerves in rotavirus disease.…”

Section: Paper II Rotavirus Infection Increases Intestinal Motility Bmentioning

confidence: 99%

“…This phenomenon may be explained by the role of nerves in controlling the gut barrier, and demonstrates the risks with conclusion from cell culture systems, lacking the nerve innervation. The vagus nerve has also been shown to affect the intestinal permeability 100,101 . Indeed, vagus nerve stimulation has been shown to attenuate disruption of tight junction in intestinal epithelium in endotoxemic mice, by a mechanism that seem to involve α7 nicotine acetylcholine receptor (α7 nAchRs) 102 .…”

Section: Paracellular Permeabilitymentioning

confidence: 99%

Rotavirus Disease Mechanisms Diarrhea, Vomiting and Inflammation : How and Why

Hagbom¹

2015

Linköping University Medical Dissertations

View full text Add to dashboard Cite

Rotavirus infections cause diarrhea and vomiting that can lead to severe dehydration. Despite extensive tissue damage and cell death, the inflammatory response is very limited. The focus of this thesis was to study pathophysiological mechanisms behind diarrhea and vomiting during rotavirus infection and also to investigate the mechanism behind the limited inflammatory response. An important discovery in this thesis was that rotavirus infection and the rotavirus toxin NSP4 stimulate release of the neurotransmitter serotonin from intestinal sensory enterochromaffin cells, in vitro and ex vivo. Interestingly, serotonin is known to be a mediator of both diarrhea and vomiting. Moreover, mice pups infected with rotavirus responded with central nervous system (CNS) activation in brain structures associated with vomiting, thus indicating a cross-talk between the gut and brain in rotavirus disease. Our finding that rotavirus infection activates the CNS led us to address the hypothesis that rotavirus infection not only activates the vagus nerve to stimulate vomiting, but also suppresses the inflammatory response via the cholinergic anti-inflammatory pathway, both of which are mediated by activated vagal afferent nerve signals into the brain stem. We found that mice lacking an intact vagus nerve, and mice lacking the α7 nicotine acetylcholine receptor (nAChR), being involved in cytokine suppression from macrophages, responded with a higher inflammatory response. Moreover, stimulated cytokine release from macrophages, by the rotavirus toxin NSP4, could be attenuated by nicotine, an agonist of the α7 nAChR. Thus, it seems most reasonable that the cholinergic anti-inflammatory pathway contributes to the limited inflammatory response during rotavirus infection. Moreover, rotavirus-infected mice displayed increased intestinal motility at the onset of diarrhea, which was not associated with increased intestinal permeability. The increased motility and diarrhea in infant mice could be attenuated by drugs acting on the enteric nervous system, indicating the importance and contribution of nerves in the rotavirus mediated disease. In conclusion, this thesis provides further insight into the pathophysiology of diarrhea and describe for the first time how rotavirus and host cross-talk to induce the vomiting reflex and limit inflammation. Results from these studies strongly support our hypothesis that serotonin and activation of the enteric nervous system and CNS contributes to diarrhea, vomiting and suppression of the inflammatory response in rotavirus disease

show abstract

“…Remarkably, vagotomised rats, do not experience sickness behavior following LPS injection 205 and experimental models have demonstrated that vagus nerve stimulation (VNS) is an effective therapy for attenuating inflammation triggered by endotoxemia 206 . In addition to promoting an anti-inflammatory cholinergic response, VNS also directly improves the integrity of the tight gap junction proteins that regulate intestinal permeability 207 . VNS has also been shown to decrease intestinal permeability and improve the integrity of the blood-brain barrier, both of which would be beneficial following TBI 208,209 .…”

Section: Vagus Nerve Stimulationmentioning

confidence: 99%

The bidirectional gut-brain-microbiota axis as a potential nexus between traumatic brain injury, inflammation, and disease

Sundman

Chen

Subbian

et al. 2017

Brain, Behavior, and Immunity

150

103

View full text Add to dashboard Cite

The bidirectional gut-brain-microbiota axis as a potential nexus between traumatic brain injury, inflammation, and disease. AbstractAs head injuries and their sequelae have become an increasingly salient matter of public health, experts in the field have made great progress elucidating the biological processes occurring within the brain at the moment of injury and throughout the recovery thereafter. Given the extraordinary rate at which our collective knowledge of neurotrauma has grown, new insights may be revealed by examining the existing literature across disciplines with a new perspective. This article will aim to expand the scope of this rapidly evolving field of research beyond the confines of the central nervous system (CNS). Specifically, we will examine the extent to which the bidirectional influence of the gut-brain axis modulates the complex biological processes occurring at the time of traumatic brain injury (TBI) and over the days, months, and years that follow. In addition to local enteric signals originating in the gut, it is well accepted that gastrointestinal (GI) physiology is highly regulated by innervation from the CNS. Conversely, emerging data suggests that the function and health of the CNS is modulated by the interaction between 1) neurotransmitters, immune signaling, hormones, and neuropeptides produced in the gut, 2) the composition of the gut microbiota, and 3) integrity of the intestinal wall serving as a barrier to the external environment. Specific to TBI, existing pre-clinical data indicates that head injuries can cause structural and functional damage to the GI tract, but research directly investigating the neuronal consequences of this intestinal damage is lacking. Despite this void, the proposed mechanisms emanating from a damaged gut are closely implicated in the inflammatory processes known to promote neuropathology in the brain following TBI, which suggests the gut-brain axis may be a therapeutic target to reduce the risk of Chronic Traumatic Encephalopathy and other neurodegenerative diseases following TBI. To better appreciate how various peripheral influences are implicated in the health of the CNS following TBI, this paper will also review the secondary biological injury mechanisms and the dynamic pathophysiological response to neurotrauma. Together, this review article will attempt to connect the dots to reveal novel insights into the bidirectional influence of the gut-brain axis and propose a conceptual model relevant to the recovery from TBI and subsequent risk for future neurological conditions.

show abstract

Efferent Vagal Nerve Stimulation Attenuates Gut Barrier Injury After Burn: Modulation of Intestinal Occludin Expression

Cited by 73 publications

References 33 publications

A Human-Specific α7-Nicotinic Acetylcholine Receptor Gene in Human Leukocytes: Identification, Regulation and the Consequences of CHRFAM7A Expression

A Human-Specific α7-Nicotinic Acetylcholine Receptor Gene in Human Leukocytes: Identification, Regulation and the Consequences of CHRFAM7A Expression

Rotavirus Disease Mechanisms Diarrhea, Vomiting and Inflammation : How and Why

The bidirectional gut-brain-microbiota axis as a potential nexus between traumatic brain injury, inflammation, and disease

Contact Info

Product

Resources

About