Angiotensin II-induced hypertensive renal inflammation is mediated through HMGB1-TLR4 signaling in rat tubulo-epithelial cells

Nair, Anand; Ebenezer, Philip J.; Saini, Yogesh; Francis, Joseph

doi:10.1016/j.yexcr.2015.05.011

Cited by 64 publications

(58 citation statements)

References 69 publications

(88 reference statements)

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“…The HMGB1–TLR4 axis is key to the inflammatory response; damaged cells and activated macrophages actively or passively release HMGB1, which induces the secretion of TNF‐α, IL‐6, and other inflammatory cytokines through signaling pathways. Early proinflammatory factors and HMGB1 itself promote the release of HMGB1 to form a loop, which amplifies the inflammatory response (Nair, Ebenezer, Saini, & Francis, 2015). TLR4 is the recognition receptor on the cell surface that identifies endogenous HMGB1.…”

Section: Discussionmentioning

confidence: 99%

High expression of the HMGB1–TLR4 axis and its downstream signaling factors in patients with Parkinson's disease and the relationship of pathological staging

Yang

Han

et al. 2018

Brain and Behavior

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ObjectiveTo detect the expression of high‐mobility group box protein 1 (HMGB1) and toll‐like receptor 4 (TLR4) and their downstream signaling factors—myeloid differentiation factor 88 (MyD88), nuclear factor kappa B (NF‐κB), and tumor necrosis factor alpha (TNF‐α)—in the sera of patients with Parkinson's disease (PD) in order to evaluate the relationship of the HMGB1–TLR4 axis with PD development and progression.MethodsThe serum HMGB1 and TLR4 protein levels of 120 patients with PD and 100 healthy volunteers were measured using double‐antibody sandwich ELISA, and their correlations with PD staging, disease duration, drug treatment effectiveness, and clinical classification were analyzed. In addition, their correlations with the key downstream factors of the HMGB1–TLR4 axis (MyD88, NF‐κB, and TNF‐α) were analyzed.ResultsHMGB1 and TLR4 expressions were higher in the peripheral blood of patients with PD than in healthy volunteers. PD patients with poor drug treatment outcomes had significantly higher HMGB1 and TLR4 expressions than PD patients with stable drug treatment outcomes. Higher HMGB1 and TLR4 expressions were found in patients at higher PD stages, and patients with >4‐year disease duration had significantly higher HMGB1 and TLR4 expressions than patients with <4‐year disease duration. No significant difference in HMGB1 and TLR4 expressions was found among patients with tremor‐dominant, akinetic‐rigid, and mixed subtypes of PD. NF‐κB and TNF‐α expressions were positively correlated with high expression of the HMGB1–TLR4 axis.ConclusionHigh expression of the HMGB1–TLR4 axis is closely associated with PD development, progression, drug treatment effectiveness, staging, and disease duration and has great significance for PD diagnosis and treatment.

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Section: Discussionmentioning

confidence: 99%

High expression of the HMGB1–TLR4 axis and its downstream signaling factors in patients with Parkinson's disease and the relationship of pathological staging

Yang

Han

et al. 2018

Brain and Behavior

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“…Macrophage mediated inflammation has been demonstrated in hypertension induced kidney damage 7 and its potential pathway may involve TLR4 activation 48 . TLR4 is expressed by macrophages and by the cells in the kidney such as, tubular epithelium, mesangial cells and podocytes 49, 50 and the latter cells show further upregulation of TLR4 to Ang-II treatment 15, 51, 52 . Inhibition of TLR4 has been shown to reduce BP and inflammation in the mesenteric arteries of SHRs 48 .…”

Section: Discussionmentioning

confidence: 99%

Toll-like Receptor 4 Deficiency Reduces Oxidative Stress and Macrophage Mediated Inflammation in Hypertensive Kidney

Pushpakumar

Ren

Kundu

et al. 2017

Sci Rep

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Oxidative stress and inflammation are integral to hypertension-induced renal injury. A unifying feature for the two components is Toll-like receptors (TLR), which are key regulators of the innate immune system. Recent studies implicate TLR4 activation and oxidative stress in cardiovascular diseases and also as a link between inflammation and hypertension. However, its role in hypertension induced renal injury remains unexplored. In the present study, we investigated whether TLR-4 deficiency reduces Ang-II-induced renal injury and fibrosis by attenuating reactive oxygen species (ROS) production and inflammation. C3H/HeOuJ mice with normal TLR-4 and C3H/HeJLps-d with dysfunctional TLR4 (TLR4 deficiency) were treated without or with Ang-II. In response to Ang-II, TLR4 deficient mice had reduced renal resistive index and increased renal cortical blood flow compared to mice with normal TLR4. Further, TLR4 deficiency reduced oxidative stress and increased antioxidant capacity (MnSOD, CuSOD and Catalase activity). TLR4 deficiency was also associated with reduced inflammation (MCP-1, MIP-2, TNF-α, IL-6 and CD68), decreased accumulation of bone marrow-derived fibroblasts and TGF-β expression. Our data suggests that in C3H/HeJLps-d mice, deficiency of functional TLR4 reduces oxidative stress and macrophage activation to decrease TGF-β-induced extracellular matrix protein deposition in the kidney in Ang-II induced hypertension.

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“…For example, tubular cell necrosis releases high-mobility group box 1 protein, an agonist to TLR2 and TLR4 and driver of inflammation during AKI. [67][68][69] Tamm-Horsfall protein/ uromodulin is exclusively expressed within the distal tubule and activates interstitial dendritic cells via TLR4 and NLRP3 whenever tubular injury promotes its leakage into the renal interstitium. 70 Toll-like receptors and inflammasomemediated immune recognition of necrotic cell death is a central element of rapidly progressive glomerulonephritis (RPGN), thrombotic microangiopathies, and acute tubular necrosis (ATN) as the release of TNF-alpha induces further cell necrosis, eg, necroptosis.…”

Section: Insufficient Clotting In Kidney Diseasementioning

confidence: 99%

Links between coagulation, inflammation, regeneration, and fibrosis in kidney pathology

Suárez-Álvarez

Liapis

Anders

2016

Laboratory Investigation

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Angiotensin II-induced hypertensive renal inflammation is mediated through HMGB1-TLR4 signaling in rat tubulo-epithelial cells

Cited by 64 publications

References 69 publications

High expression of the HMGB1–TLR4 axis and its downstream signaling factors in patients with Parkinson's disease and the relationship of pathological staging

High expression of the HMGB1–TLR4 axis and its downstream signaling factors in patients with Parkinson's disease and the relationship of pathological staging

Toll-like Receptor 4 Deficiency Reduces Oxidative Stress and Macrophage Mediated Inflammation in Hypertensive Kidney

Links between coagulation, inflammation, regeneration, and fibrosis in kidney pathology

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