ArticleThe Journal of biological chemistry2012
Kuppfer cells trigger nonalcoholic steatohepatitis development in diet-induced mouse model through tumor necrosis factor-α production.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 255 papers, 1 of them a synthesis that pooled it.
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
255 citing papers in PubMed, 1 synthesis or guideline pooled it, 409 citations in OpenAlex.
- Risk of dementia or cognitive impairment in non-alcoholic fatty liver disease: A systematic review and meta-analysis.Frontiers in aging neuroscience · 2022Pooled it
- Toll-like receptor 2 drives liver senescence and fibrosis in aging through gut-derived microbial signaling.Cellular & molecular biology letters · 2026Article
- Mechanistic insights into the liver-brain axis during chronic liver disease.Nature reviews. Gastroenterology & hepatology · 2026Review
- Integrating multi-omics and machine learning systematically deciphers cellular heterogeneity and fibrotic regulatory networks in the progression from MASLD to MASH.NPJ digital medicine · 2026Article
- The Role of Kupffer Cells and Liver Macrophages in the Pathogenesis of Metabolic Dysfunction-Associated Steatotic Liver Disease.Biomedicines · 2026Review
- Significance of fatty acid metabolism regulators in the diagnosis and subtype classification in non-alcoholic fatty liver disease.Frontiers in cell and developmental biology · 2026Article
- The gene regulatory networks shaping macrophage plasticity and altered function in fibrosis.Frontiers in immunology · 2026Review
- Fatty acid metabolism and lipid channeling in macrophages: mechanisms of inflammation, resolution, and lipotoxicity.Frontiers in immunology · 2026Review
- Maresin 1 induces resolution of hepatic fibrosis through RORα-dependent reprogramming of resident macrophages.Frontiers in pharmacology · 2026Article
- Myeloid HDAC7 drives liver inflammation and systemic glucose dysregulation during diet-induced obesity.Clinical & translational immunology · 2026Article
- CD163 Expression Protects Against Early Hepatic Steatosis in Western Diet-Fed Male Mice.Gastro hep advances · 2026Article
- Targeting macrophages in liver fibrosis.Frontiers in immunology · 2026Review
- Rheumatoid Factor Beyond Rheumatoid Arthritis: A Potential Marker of Cardiometabolic and Hepatic Risk.Biologics : targets & therapy · 2026Review
- Molecular mechanisms mediated by liquid-liquid phase separation in chronic liver disease progression.iScience · 2025Review
- Myeloid cells in chronic liver inflammation.Cellular & molecular immunology · 2025Review
- α-Lack-SPI Alleviates MASLD in Rats via Regulating Hepatic Lipid Accumulation and Inflammation.Nutrients · 2025Article
- The current findings on the gut-liver axis and the molecular basis of NAFLD/NASH associated with gut microbiome dysbiosis.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- CD44 in Group 1 Innate Lymphoid Cells Impacts the Development and Progression of Steatohepatitis.Liver international : official journal of the International Association for the Study of the Liver · 2025Article
- Palmitic acid reduces LDLR-dependent uptake of macrophage-derived extracellular vesicles by hepatoma cells.Non-coding RNA research · 2025Article
- The immunological interface: dendritic cells as key regulators in metabolic dysfunction-associated steatotic liver disease.FEBS letters · 2025Review
195 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundThe mechanisms triggering nonalcoholic steatohepatitis (NASH) remain poorly defined.
resultsKupffer cells are the first responding cells to hepatocyte injuries, leading to TNFα production, chemokine induction, and monocyte recruitment. The silencing of TNFα in myeloid cells reduces NASH progression.
conclusionIncrease of TNFα-producing Kupffer cells is crucial for triggering NASH via monocyte recruitment. SIGNIFICANCE: Myeloid cells-targeted silencing of TNFα might be a tenable therapeutic approach. Nonalcoholic steatohepatitis (NASH), characterized by lipid deposits within hepatocytes (steatosis), is associated with hepatic injury and inflammation and leads to the development of fibrosis, cirrhosis, and hepatocarcinoma. However, the pathogenic mechanism of NASH is not well understood. To determine the role of distinct innate myeloid subsets in the development of NASH, we examined the contribution of liver resident macrophages (i.e. Kupffer cells) and blood-derived monocytes in triggering liver inflammation and hepatic damage. Employing a murine model of NASH, we discovered a previously unappreciated role for TNFα and Kupffer cells in the initiation and progression of NASH. Sequential depletion of Kupffer cells reduced the incidence of liver injury, steatosis, and proinflammatory monocyte infiltration. Furthermore, our data show a differential contribution of Kupffer cells and blood monocytes during the development of NASH; Kupffer cells increased their production of TNFα, followed by infiltration of CD11b(int)Ly6C(hi) monocytes, 2 and 10 days, respectively, after starting the methionine/choline-deficient (MCD) diet. Importantly, targeted knockdown of TNFα expression in myeloid cells decreased the incidence of NASH development by decreasing steatosis, liver damage, monocyte infiltration, and the production of inflammatory chemokines. Our findings suggest that the increase of TNFα-producing Kupffer cells in the liver is crucial for the early phase of NASH development by promoting blood monocyte infiltration through the production of IP-10 and MCP-1.
Indexed as
Identifiers
What OpenQuestion 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 OpenQuestion graph.