ArticleJournal of immunology (Baltimore, Md. : 1950)2013
Calpastatin prevents NF-κB-mediated hyperactivation of macrophages and attenuates colitis.
Article in Journal of immunology (Baltimore, Md. : 1950), 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
What it found
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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.
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Who cites it
21 citing papers in PubMed, 32 citations in OpenAlex.
- Protein quantitative trait locus study in obesity during weight-loss identifies a leptin regulator.Nature communications · 2017Trial
- Calpain-2 facilitates infection of the intracellular bacteria Listeria monocytogenes and invasion intestinal immune barrier by impairing nitric oxide homeostasis.Journal of advanced research · 2026Article
- Article
- Proteases in intestinal health and disease.Nature reviews. Gastroenterology & hepatology · 2026Review
- Gene‒Environment Interaction Between CAST Gene and Eye-Rubbing in the Chinese Keratoconus Cohort Study: A Case-Only Study.Investigative ophthalmology & visual science · 2024Article
- A common human MLKL polymorphism confers resistance to negative regulation by phosphorylation.Nature communications · 2023Article
- Selenoprotein I deficiency in T cells promotes differentiation into tolerant phenotypes while decreasing Th17 pathology.Journal of leukocyte biology · 2022Article
- Macrophage orchestration of epithelial and stromal cell homeostasis in the intestine.Journal of leukocyte biology · 2022Review
- Molecular Mechanisms by Which Selenoprotein K Regulates Immunity and Cancer.Biological trace element research · 2019Review
- Use of a Mouse Model and Human Umbilical Vein Endothelial Cells to Investigate the Effect of Arsenic Exposure on Vascular Endothelial Function and the Associated Role of Calpains.Environmental health perspectives · 2019Article
- The methylome of the celiac intestinal epithelium harbours genotype-independent alterations in the HLA region.Scientific reports · 2019Article
- Mechanistic Role of the Calcium-Dependent Protease Calpain in the Endothelial Dysfunction Induced by MPO (Myeloperoxidase).Hypertension (Dallas, Tex. : 1979) · 2018Article
- Calpain-2 inhibitor treatment preferentially reduces tumor progression for human colon cancer cells expressing highest levels of this enzyme.Cancer medicine · 2018Article
- Calpain Inhibition Attenuates Adipose Tissue Inflammation and Fibrosis in Diet-induced Obese Mice.Scientific reports · 2017Article
- Selenium nanoparticles decorated with Ulva lactuca polysaccharide potentially attenuate colitis by inhibiting NF-κB mediated hyper inflammation.Journal of nanobiotechnology · 2017Article
- Adiposity-Dependent Regulatory Effects on Multi-tissue Transcriptomes.American journal of human genetics · 2016Article
- MALT1 inhibitors prevent the development of DSS-induced experimental colitis in mice via inhibiting NF-κB and NLRP3 inflammasome activation.Oncotarget · 2016Article
- Leukocyte Calpain Deficiency Reduces Angiotensin II-Induced Inflammation and Atherosclerosis But Not Abdominal Aortic Aneurysms in Mice.Arteriosclerosis, thrombosis, and vascular biology · 2016Article
- Calpain-2 Inhibitor Therapy Reduces Murine Colitis and Colitis-associated Cancer.Inflammatory bowel diseases · 2015Article
- α1-antitrypsin modulates microglial-mediated neuroinflammation and protects microglial cells from amyloid-β-induced toxicity.Journal of neuroinflammation · 2014Article
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 4 countries.
Funding
Abstract
Calpain enzymes proteolytically modulate cellular function and have been implicated in inflammatory diseases. In this study, we found that calpain levels did not differ between intestinal tissues from inflammatory bowel disease (IBD) patients and healthy controls, but IBD tissues showed increased levels of the endogenous calpain inhibitor, calpastatin (CAST). To investigate the role of CAST in the immune system during IBD, mice were x-ray irradiated, reconstituted with either CAST-knockout (KO) or wild-type (WT) bone marrow, and subjected to dextran sulfate sodium-induced colitis. CAST-KO recipients with induced colitis exhibited more severe weight loss, bloody diarrhea, and anemia compared with WT controls. Histological evaluation of colons from KO recipients with colitis revealed increased inflammatory pathology. Macrophages purified from the colons of KO recipients had higher IL-6, TNF-α, and IFN-γ mRNA levels compared with WT controls. Mechanistic investigations using small interfering RNA and KO bone marrow to generate CAST-deficient macrophages showed that CAST deficiency during activation with bacterial pathogen associated molecular patterns, including heat-killed Enterococcus faecalis or CpG DNA, led to increased IκB cleavage, NF-κB nuclear localization, and IL-6 and TNF-α secretion. Thus, CAST plays a central role in regulating macrophage activation and limiting pathology during inflammatory disorders like IBD.
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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.