ArticleJournal of the American Society of Nephrology : JASN2016
IL-6 Trans-Signaling Drives Murine Crescentic GN.
Article in Journal of the American Society of Nephrology : JASN, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
30 citing papers in PubMed, 59 citations in OpenAlex.
- Nonspecific Inhibition of IL6 Family Cytokine Signalling by Soluble gp130.International journal of molecular sciences · 2024Article
- IL-6 and diabetic kidney disease.Frontiers in immunology · 2024Review
- The Immunobiological Agents for Treatment of Antiglomerular Basement Membrane Disease.Medicina (Kaunas, Lithuania) · 2023Review
- Targeting IL-6 trans-signalling: past, present and future prospects.Nature reviews. Immunology · 2023Review
- Dissecting Interleukin-6 Classic and Trans-signaling in Inflammation and Cancer.Methods in molecular biology (Clifton, N.J.) · 2023Article
- LC-MS/MS based metabolomics and proteomics reveal candidate biomarkers and molecular mechanism of early IgA nephropathy.Clinical proteomics · 2022Article
- Interleukin 6 mediated activation of the mineralocorticoid receptor in the aldosterone-sensitive distal nephron.American journal of physiology. Cell physiology · 2022Article
- Clinical value of urinary cytokines/chemokines as prognostic markers in patients with crescentic glomerulonephritis.Scientific reports · 2022Article
- Cyclic swelling enabled, electrically conductive 3D porous structures for microfluidic urinalysis devices.Extreme Mechanics Letters · 2022Article
- Immunomodulatory agents for COVID-19 treatment: possible mechanism of action and immunopathology features.Molecular and cellular biochemistry · 2022Review
- Recent advances in antibody-based immunotherapy strategies for COVID-19.Journal of cellular biochemistry · 2021Review
- ADAMs family in kidney physiology and pathology.EBioMedicine · 2021Review
- A potential pathogenic role of interleukin-6 in a child with ANCA-negative pauci-immune crescentic glomerulonephritis: case report and literature review.BMC nephrology · 2021Review
- Key metalloproteinase-mediated pathways in the kidney.Nature reviews. Nephrology · 2021Review
- Insights into forsythia honeysuckle (Lianhuaqingwen) capsules: A Chinese herbal medicine repurposed for COVID-19 pandemic.Phytomedicine plus : international journal of phytotherapy and phytopharmacology · 2021Review
- Emerging New Approaches in Desensitization: Targeted Therapies for HLA Sensitization.Frontiers in immunology · 2021Review
- Abnormal immunity of non-survivors with COVID-19: predictors for mortality.Infectious diseases of poverty · 2020Observational
- Tocilizumab: A Therapeutic Option for the Treatment of Cytokine Storm Syndrome in COVID-19.Archives of medical research · 2020Article
- Rational Use of Tocilizumab in the Treatment of Novel Coronavirus Pneumonia.Clinical drug investigation · 2020Review
- Tocilizumab monotherapy uncovered the role of the CCL22/17-CCR4Clinical & translational immunology · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 5 institutions in 4 countries.
Funding
Abstract
The role of IL-6 signaling in renal diseases remains controversial, with data describing both anti-inflammatory and proinflammatory effects. IL-6 can act via classic signaling, engaging its two membrane receptors gp130 and IL-6 receptor (IL-6R). Alternatively, IL-6 trans-signaling requires soluble IL-6R (sIL-6R) to act on IL-6R-negative cells that express gp130. Here, we characterize the role of both pathways in crescentic nephritis. Patients with crescentic nephritis had significantly elevated levels of IL-6 in both serum and urine. Similarly, nephrotoxic serum-induced nephritis (NTN) in BALB/c mice was associated with elevated serum IL-6 levels. Levels of serum sIL-6R and renal downstream signals of IL-6 (phosphorylated signal transducer and activator of transcription 3, suppressor of cytokine signaling 3) increased over time in this model. Simultaneous inhibition of both IL-6 signaling pathways using anti-IL-6 antibody did not have a significant impact on NTN severity. In contrast, specific inhibition of trans-signaling using recombinant sgp130Fc resulted in milder disease. Vice versa, specific activation of trans-signaling using a recombinant IL-6-sIL-6R fusion molecule (Hyper-IL-6) significantly aggravated NTN and led to increased systolic BP in NTN mice. This correlated with increased renal mRNA synthesis of the Th17 cell cytokine IL-17A and decreased synthesis of resistin-like alpha (RELMalpha)-encoding mRNA, a surrogate marker of lesion-mitigating M2 macrophage subtypes. Collectively, our data suggest a central role for IL-6 trans-signaling in crescentic nephritis and offer options for more effective and specific therapeutic interventions in the IL-6 system.
Indexed as
Identifiers
What Socratic holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.