ArticleCellular & molecular immunology2021
The inhibitor effect of RKIP on inflammasome activation and inflammasome-dependent diseases.
Article in Cellular & molecular immunology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 38 citations in OpenAlex.
- NLR Inflammasomes in Viral Infections: From Molecular Mechanisms to Therapeutic Interventions.Viruses · 2026Review
- Brain-Derived Neurotrophic Factor Deficiency Exacerbates Innate Immune Responses by Enhancing NLRP3 Inflammasome Activation and GSDMD-Mediated Pyroptosis in Mice.Medicina (Kaunas, Lithuania) · 2026Article
- Expression Analysis of Selected microRNAs in Diabetes Mellitus Visceral Fat Tissues.Journal of obesity · 2026Article
- Specific inhibition of NLRP3 inflammasome by a Smurf1 inhibitorOpen medicine (Warsaw, Poland) · 2026Article
- Diet-induced RKIP downregulation disrupts PC/PE-ER homeostasis to drive MASLD.Nature communications · 2025Article
- Activation and regulation of NAIP/NLRC4 and NLRP3 inflammasomes during Salmonella infection: mechanisms and therapeutic implications.Molecular biology reports · 2025Review
- RKIP regulates bone marrow macrophage differentiation to mediate osteoclastogenesis and H-type vessel formation.Nature communications · 2025Article
- Unraveling the RKIP-YY1 axis: immune crosstalk in the pathogenesis of metabolic disorders.Frontiers in immunology · 2025Review
- Paraptosis-A Distinct Pathway to Cell Death.International journal of molecular sciences · 2024Review
- NLRP inflammasomes in health and disease.Molecular biomedicine · 2024Review
- Transcriptomic Analysis of THP-1 Cells Exposed by Monosodium Urate Reveals Key Genes Involved in Gout.Combinatorial chemistry & high throughput screening · 2024Article
- Muscone ameliorates myocardial ischemia‒reperfusion injury by promoting myocardial glycolysis.Heliyon · 2023Article
- 1,25(OH)Experimental and therapeutic medicine · 2023Article
- Review
- The Combination of Natural Molecules Naringenin, Hesperetin, Curcumin, Polydatin and Quercetin Synergistically Decreases SEMA3E Expression Levels and DPPIV Activity in In Vitro Models of Insulin Resistance.International journal of molecular sciences · 2023Article
- Changes in Expression of Tumor Suppressor Gene RKIP Impact How Cancers Interact with Their Complex Environment.Cancers · 2023Review
- RKIP suppresses the influenza A virus‑induced airway inflammatory response via the ERK/MAPK pathway.International journal of molecular medicine · 2023Article
- Activation of RKIP Binding ASC Attenuates Neuronal Pyroptosis and Brain Injury via Caspase-1/GSDMD Signaling Pathway After Intracerebral Hemorrhage in Mice.Translational stroke research · 2022Article
- Selective EZH2 inhibitor zld1039 alleviates inflammation in cisplatin-induced acute kidney injury partially by enhancing RKIP and suppressing NF-κB p65 pathway.Acta pharmacologica Sinica · 2022Article
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Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Aberrant inflammasome activation contributes to the pathogenesis of various human diseases, including atherosclerosis, gout, and metabolic disorders. Elucidation of the underlying mechanism involved in the negative regulation of the inflammasome is important for developing new therapeutic targets for these diseases. Here, we showed that Raf kinase inhibitor protein (RKIP) negatively regulates the activation of the NLRP1, NLRP3, and NLRC4 inflammasomes. RKIP deficiency enhanced caspase-1 activation and IL-1β secretion via NLRP1, NLRP3, and NLRC4 inflammasome activation in primary macrophages. The overexpression of RKIP in THP-1 cells inhibited NLRP1, NLRP3, and NLRC4 inflammasome activation. RKIP-deficient mice showed increased sensitivity to Alum-induced peritonitis and Salmonella typhimurium-induced inflammation, indicating that RKIP inhibits NLRP3 and NLRC4 inflammasome activation in vivo. Mechanistically, RKIP directly binds to apoptosis-associated speck-like protein containing a caspase-recruitment domain (ASC) and competes with NLRP1, NLRP3, or NLRC4 to interact with ASC, thus interrupting inflammasome assembly and activation. The depletion of RKIP aggravated inflammasome-related diseases such as monosodium urate (MSU)-induced gouty arthritis and high-fat diet (HFD)-induced metabolic disorders. Furthermore, the expression of RKIP was substantially downregulated in patients with gouty arthritis or type 2 diabetes (T2D) compared to healthy controls. Collectively, our findings suggest that RKIP negatively regulates NLRP1, NLRP3, and NLRC4 inflammasome activation and is a potential therapeutic target for the treatment of inflammasome-related diseases.
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Registered trials
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