Over-salting ruins the balance of the immune menu

Min, Booki; Fairchild, Robert L.

doi:10.1172/jci84690

Cited by 15 publications

(11 citation statements)

References 14 publications

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“…As previously demonstrated, increased plasma Na + has high pro-inflammatory potential through both enhancing proinflammatory responses and impairing regulatory mechanisms13738. It turned out that the vascular endothelium is sensitive to a small rise in Na + concentrations, such that a defined range of extracellular Na + concentrations tightly links the mechanical properties to NO production6.…”

Section: Discussionmentioning

confidence: 95%

Nanomechanics of the endothelial glycocalyx contribute to Na+-induced vascular inflammation

Schierke

Wyrwoll

Wisdorf

et al. 2017

Sci Rep

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High dietary salt (NaCl) is a known risk factor for cardiovascular pathologies and inflammation. High plasma Na+ concentrations (high Na+) have been shown to stiffen the endothelial cortex and decrease nitric oxide (NO) release, a hallmark of endothelial dysfunction. Here we report that chronic high Na+ damages the endothelial glycocalyx (eGC), induces release of inflammatory cytokines from the endothelium and promotes monocyte adhesion. Single cell force spectroscopy reveals that high Na+ enhances vascular adhesion protein-1 (VCAM-1)-dependent adhesion forces between monocytes and endothelial surface, giving rise to increased numbers of adherent monocytes on the endothelial surface. Mineralocorticoid receptor antagonism with spironolactone prevents high Na+-induced eGC deterioration, decreases monocyte-endothelium interactions, and restores endothelial function, indicated by increased release of NO. Whereas high Na+ decreases NO release, it induces endothelial release of the pro-inflammatory cytokines IL-1ß and TNFα. However, in contrast to chronic salt load (hours), in vivo and in vitro, an acute salt challenge (minutes) does not impair eGC function. This study identifies the eGC as important mediator of inflammatory processes and might further explain how dietary salt contributes to endothelialitis and cardiovascular pathologies by linking endothelial nanomechanics with vascular inflammation.

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Section: Discussionmentioning

confidence: 95%

Nanomechanics of the endothelial glycocalyx contribute to Na+-induced vascular inflammation

Schierke

Wyrwoll

Wisdorf

et al. 2017

Sci Rep

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“…However, NaCl itself is proinflammatory and has been shown to induce T H 17 cells while conversely inhibiting forkhead box protein 3 + regulatory T-cell function 38 , 39 and to also activate inflammatory cascades in monocytes and bone marrow–derived macrophages in vitro . 40 , 41 The saline control that we used in the current study contained 0.9% NaCl, which is similar to the concentration used in the diluent of the VZV skin test antigen (0.68% NaCl). Therefore a component of the transcriptional response of old subjects to VZV antigen would also include a response to NaCl in the diluent that might hinder the induction of antigen-specific immunity in old subjects.…”

Section: Discussionmentioning

confidence: 99%

Enhancement of cutaneous immunity during aging by blocking p38 mitogen-activated protein (MAP) kinase–induced inflammation

Vukmanovic‐Stejic

Chambers

Suárez‐Fariñas

et al. 2018

Journal of Allergy and Clinical Immunology

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BackgroundImmunity decreases with age, which leads to reactivation of varicella zoster virus (VZV). In human subjects age-associated immune changes are usually measured in blood leukocytes; however, this might not reflect alterations in tissue-specific immunity.ObjectivesWe used a VZV antigen challenge system in the skin to investigate changes in tissue-specific mechanisms involved in the decreased response to this virus during aging.MethodsWe assessed cutaneous immunity based on the extent of erythema and induration after intradermal VZV antigen injection. We also performed immune histology and transcriptomic analyses on skin biopsy specimens taken from the challenge site in young (<40 years) and old (>65 years) subjects.ResultsOld human subjects exhibited decreased erythema and induration, CD4+ and CD8+ T-cell infiltration, and attenuated global gene activation at the site of cutaneous VZV antigen challenge compared with young subjects. This was associated with increased sterile inflammation in the skin in the same subjects related to p38 mitogen-activated protein kinase–related proinflammatory cytokine production (P < .0007). We inhibited systemic inflammation in old subjects by means of pretreatment with an oral small-molecule p38 mitogen-activated protein kinase inhibitor (Losmapimod; GlaxoSmithKline, Brentford, United Kingdom), which reduced both serum C-reactive protein levels and peripheral blood monocyte secretion of IL-6 and TNF-α. In contrast, cutaneous responses to VZV antigen challenge were increased significantly in the same subjects (P < .0003).ConclusionExcessive inflammation in the skin early after antigen challenge retards antigen-specific immunity. However, this can be reversed by inhibition of inflammatory cytokine production that can be used to promote vaccine efficacy and the treatment of infections and malignancy during aging.

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“…Studies have shown that an HSD can induce human circulating monocyte proinflammatory activation and is associated with monocyte-platelet aggregation [13]. Moreover, the activation and function of dendritic cells, M1 macrophages are stimulated on an HSD, while M2 macrophages are blunted found in vitro and in vivo [14][15][16], accompanied by increased activation of pro-IL-1β, nuclear factor-κB, and p38/mitogen-activated protein kinase (MAPK)-dependent nuclear factor of the activated T-cell 5 (NFAT5) signaling, and elevated NO production [14,17,18]. Interestingly, studies found that macrophages in turn might be pivotal regulators of salt homeostasis by a TonEBP-VEGF-C-dependent buffering mechanism, since the NaCl hypertonicity was proved to stimulate macrophages to migrate in the direction of excess salt concentration in vitro [19].…”

Section: Hsd Influence the Immune Systemmentioning

confidence: 99%

“…These proteins are important in the pyrimidine metabolism, ATP binding, materials transferring, cell cycle, and cell division. On the other hand, the HSD was found to exert a synergistic effect with Helicobacter pylori on the development of gastritis [7,8] and H. pylori-associated carcinogenesis [15,20,23,48]. Studies demonstrated that HSD can alter H. pylori gene expression while modulating H. pylori-induced virulence factors such as cytotoxinassociated gene A (CagA) [45] and vacuolating cytotoxin (VacA) [21,23,49].…”

Section: Hsd Alters the Gut Microbiota Functionmentioning

confidence: 99%

High-Salt Diet Gets Involved in Gastrointestinal Diseases through the Reshaping of Gastroenterological Milieu

Sun

Guo

et al. 2018

Digestion

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Background: Gastrointestinal (GI) diseases are known to be largely influenced by one’s lifestyle and dietary uptake. A high-salt diet (HSD) is well recognized as a risk factor for cardiovascular complications, hypertension, and metabolic syndromes. However, the relationship between an HSD and the GI system, which is the compartment that comes in direct contact with exogenous stimulants, has not been fully explored. Aims: We seek to better understand the complexity of the pathogenic effects of an HSD in the context of GI disorders. Methods: By searching the PubMed and Web of science, the review of literature was performed using keywords: high-salt and GI, high-salt and immunity, salt and microbiota, salt and hormone. Results: In this review, we concluded that high-salt intake potentially perturbs the local immune homeostasis, alters the gut microbiota composition and function, and affects the endocrine hormone profiling in the GI system. Conclusion: HSD might get involved in GI diseases through the reshaping of gastroenterological milieu, which could help to better understand the complexity of the pathogenic effects of an HSD in the context of GI disorders.

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Over-salting ruins the balance of the immune menu

Abstract: C o m m e n t a r y 4 0 0 2

Cited by 15 publications

References 14 publications

Nanomechanics of the endothelial glycocalyx contribute to Na+-induced vascular inflammation

Nanomechanics of the endothelial glycocalyx contribute to Na+-induced vascular inflammation

Enhancement of cutaneous immunity during aging by blocking p38 mitogen-activated protein (MAP) kinase–induced inflammation

High-Salt Diet Gets Involved in Gastrointestinal Diseases through the Reshaping of Gastroenterological Milieu

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