Tumor necrosis factor-α: regulation of renal function and blood pressure

Ramseyer, Vanesa D.; Garvin, Jeffrey L.

doi:10.1152/ajprenal.00557.2012

Cited by 143 publications

(121 citation statements)

References 165 publications

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“…We speculate that the effects of IL-1 on renal sodium handling may be bi-phasic in which mild IL-1 elevations occurring in hypertension favor salt retention whereas fulminant IL-1 elevations during sepsis trigger natriuresis with a risk of circulatory collapse (Caverzasio et al, 1987). Such a phenomenon has been described with another pro-inflammatory cytokine, TNF (Ramseyer and Garvin, 2013). The apparent discrepancies in IL-1 actions could also be related to the source and distribution of IL-1 within the kidney as macrophages infiltrating the interstitium are likely a prominent source of intra-renal IL-1 in hypertension.…”

Section: Discussionmentioning

confidence: 95%

Interleukin-1 Receptor Activation Potentiates Salt Reabsorption in Angiotensin II-Induced Hypertension via the NKCC2 Co-transporter in the Nephron

et al. 2016

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Summary Hypertension is among the most prevalent and catastrophic chronic diseases worldwide. While the efficacy of renin angiotensin system (RAS) blockade in lowering blood pressure illustrates that the RAS is broadly activated in human hypertension, the frequent failure of RAS inhibition to prevent or reverse hypertensive organ damage highlights the need for novel therapies to combat RAS-dependent hypertension. We previously discovered elevated levels of the macrophage cytokine IL-1 in the kidney in a murine model of RAS-mediated hypertension. Here we report that IL-1 receptor (IL-1R1) deficiency or blockade limits blood pressure elevation in this model by mitigating sodium reabsorption via the NKCC2 co-transporter in the nephron. In this setting, IL-1R1 activation prevents intra-renal myeloid cells from maturing into Ly6C+Ly6G− macrophages that elaborate nitric oxide, a natriuretic hormone that suppresses NKCC2 activity. By revealing how the innate immune system regulates tubular sodium transport, these experiments should lead to new immunomodulatory anti-hypertensive therapies.

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Section: Discussionmentioning

confidence: 95%

Interleukin-1 Receptor Activation Potentiates Salt Reabsorption in Angiotensin II-Induced Hypertension via the NKCC2 Co-transporter in the Nephron

et al. 2016

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“…Ramseyer and Garvin have recently reviewed this topic. 60 As in the case of the endothelium, TNFα decreases eNOS expression in medullary thick ascending limb cells within 24 hours of exposure in a Rho-kinase dependent manner. 61 NO inhibits sodium reabsorption at several sites along the renal tubule including the mTAL and collecting duct, and its loss would therefore lead to sodium retention.…”

Section: Cytokines Contributing To Hypertensionmentioning

confidence: 91%

Inflammation, Immunity, and Hypertensive End-Organ Damage

McMaster

Kirabo

Madhur

et al. 2015

Circulation Research

582

459

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For more than 50 years, it has been recognized that immunity contributes to hypertension. Recent data have defined an important role of T cells and various T cell-derived cytokines in several models of experimental hypertension. These studies have shown that stimuli like angiotensin II, DOCA-salt and excessive catecholamines lead to formation of effector like T cells that infiltrate the kidney and perivascular regions of both large arteries and arterioles. There is also accumulation of monocyte/macrophages in these regions. Cytokines released from these cells, including IL-17, IFN-γ, TNFα and IL-6 promote both renal and vascular dysfunction and damage, leading to enhanced sodium retention and increased systemic vascular resistance. The renal effects of these cytokines remain to be fully defined, but include enhanced formation of angiotensinogen, increased sodium reabsorption and increased renal fibrosis. Very recent experiments have defined a link between oxidative stress and immune activation in hypertension. These have shown that hypertension is associated with formation of reactive oxygen species in dendritic cells that lead to formation of gamma ketoaldehydes, or isoketals. These rapidly adduct to protein lysines and are presented by dendritic cells as neoantigens that activate T cells and promote hypertension. Thus, cells of both the innate and adaptive immune system contribute to end-organ damage and dysfunction in hypertension. Therapeutic interventions to reduce activation of these cells may prove beneficial in reducing end-organ damage and preventing consequences of hypertension including myocardial infarction, heart failure, renal failure and stroke.

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“…The levels of TNF-α are increased in the airway tissues of asthmatic subjects and TNF-α expression has been seen to be up-regulated in alveolar macrophages, mast cells, and bronchial epithelial cells [69,70]. TNF-α was also found to be higher in concentration in chronic inflammatory states, such as hypertension, and is implicated in both increases and decreases in blood pressure [71]. It is interesting that the TNF-α, which has a high centrality, turned out to be connected in the regulatory network with NF-kappaB, which also has a high centrality value (Fig.…”

Section: Associative Gene Network Of Asthma and Hypertensionmentioning

confidence: 99%

Novel candidate genes important for asthma and hypertension comorbidity revealed from associative gene networks

et al. 2018

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Background: Hypertension and bronchial asthma are a major issue for people's health. As of 2014, approximately one billion adults, or~22% of the world population, have had hypertension. As of 2011, 235-330 million people globally have been affected by asthma and approximately 250,000-345,000 people have died each year from the disease. The development of the effective treatment therapies against these diseases is complicated by their comorbidity features. This is often a major problem in diagnosis and their treatment. Hence, in this study the bioinformatical methodology for the analysis of the comorbidity of these two diseases have been developed. As such, the search for candidate genes related to the comorbid conditions of asthma and hypertension can help in elucidating the molecular mechanisms underlying the comorbid condition of these two diseases, and can also be useful for genotyping and identifying new drug targets. Results: Using ANDSystem, the reconstruction and analysis of gene networks associated with asthma and hypertension was carried out. The gene network of asthma included 755 genes/proteins and 62,603 interactions, while the gene network of hypertension -713 genes/proteins and 45,479 interactions. Two hundred and five genes/proteins and 9638 interactions were shared between asthma and hypertension. An approach for ranking genes implicated in the comorbid condition of two diseases was proposed. The approach is based on nine criteria for ranking genes by their importance, including standard methods of gene prioritization (Endeavor, ToppGene) as well as original criteria that take into account the characteristics of an associative gene network and the presence of known polymorphisms in the analysed genes. According to the proposed approach, the genes IL10, TLR4, and CAT had the highest priority in the development of comorbidity of these two diseases. Additionally, it was revealed that the list of top genes is enriched with apoptotic genes and genes involved in biological processes related to the functioning of central nervous system.

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Tumor necrosis factor-α: regulation of renal function and blood pressure

Abstract: Ramseyer VD, Garvin JL. Tumor necrosis factor-␣: regulation of renal function and blood pressure.

Cited by 143 publications

References 165 publications

Interleukin-1 Receptor Activation Potentiates Salt Reabsorption in Angiotensin II-Induced Hypertension via the NKCC2 Co-transporter in the Nephron

Interleukin-1 Receptor Activation Potentiates Salt Reabsorption in Angiotensin II-Induced Hypertension via the NKCC2 Co-transporter in the Nephron

Inflammation, Immunity, and Hypertensive End-Organ Damage

Novel candidate genes important for asthma and hypertension comorbidity revealed from associative gene networks

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