ArticleThe Journal of biological chemistry2014
Lipopolysaccharide decreases single immunoglobulin interleukin-1 receptor-related molecule (SIGIRR) expression by suppressing specificity protein 1 (Sp1) via the Toll-like receptor 4 (TLR4)-p38 pathway in monocytes and neutrophils.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 60 citations in OpenAlex.
- IL-37/IL-1R8 axis: a novel major mechanism of control at the interface between tumor and immune cells.Oncoimmunology · 2026Review
- The central function and specific molecular mechanisms of the TLR4 pathway underlying impaired intestinal barrier in necrotizing enterocolitis.Biochemistry and biophysics reports · 2026Review
- Characteristics of T-Cells Expressing IL-37 and Its Receptors in Inflammatory Bowel Disease.International journal of molecular sciences · 2026Article
- SIGIRR: An Orphan Receptor Mediating Anti-inflammatory Actions.Expert reviews in molecular medicine · 2025Review
- The nuclear cytokine IL-37a controls lethal cytokine storms primarily via IL-1R8-independent transcriptional upregulation of PPARγ.Cellular & molecular immunology · 2023Article
- SIGIRR deficiency contributes to CD4 T cell abnormalities by facilitating the IL1/C/EBPβ/TNF-α signaling axis in rheumatoid arthritis.Molecular medicine (Cambridge, Mass.) · 2022Article
- A Splice Switch in SIGIRR Causes a Defect of IL-37-Dependent Anti-Inflammatory Activity in Cystic Fibrosis Airway Epithelial Cells.International journal of molecular sciences · 2022Article
- IL-1R8 as Pathoimmunological Marker for Severity of Canine Chronic Enteropathy.Veterinary sciences · 2022Article
- Negative Regulation of the IL-1 System by IL-1R2 and IL-1R8: Relevance in Pathophysiology and Disease.Frontiers in immunology · 2022Review
- Negative Effects of SIGIRR on TRAF6 Ubiquitination in Acute Lung Injury In Vitro.Journal of immunology research · 2020Article
- The deubiquitinase USP13 stabilizes the anti-inflammatory receptor IL-1R8/Sigirr to suppress lung inflammation.EBioMedicine · 2019Article
- IL-33/ST2 signalling and crosstalk with FcεRI and TLR4 is targeted by the parasitic worm product, ES-62.Scientific reports · 2018Article
- Tuning inflammation and immunity by the negative regulators IL-1R2 and IL-1R8.Immunological reviews · 2018Review
- A novel role for myeloid cell-specific neuropilin 1 in mitigating sepsis.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2017Article
- Pharmacological and genetic reappraisals of protease and oxidative stress pathways in a mouse model of obstructive lung diseases.Scientific reports · 2016Article
- Cytokine decoy and scavenger receptors as key regulators of immunity and inflammation.Cytokine · 2016Article
- Adipose tissue-derived stem cells suppress hypertrophic scar fibrosis via the p38/MAPK signaling pathway.Stem cell research & therapy · 2016Article
- MMP-9 signaling in the left ventricle following myocardial infarction.American journal of physiology. Heart and circulatory physiology · 2016Review
- Regulatory Role of IL-1R8 in Immunity and Disease.Frontiers in immunology · 2016Review
Corrections and comments
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Authors and funding
13 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Single immunoglobulin interleukin-1 receptor-related molecule (SIGIRR) is one of the immunoglobulin-like membrane proteins that is crucial for negative regulation of toll-like receptor 4 (TLR4) and interleukin-1 receptor. Despite the importance of understanding its expression and function, knowledge is limited on the regulatory mechanism in the epithelial tissues, such as the liver, lung, and gut, where its predominant expression is originally described. Here, we found expression of SIGIRR in non-epithelial innate immune cells, including primary peripheral blood monocytes, polymorphonuclear neutrophils, monocytic RAW264 cells, and neutrophilic-differentiated HL-60 cells. Consistent with previous findings in epithelial tissues, SIGIRR gene and protein expression were also down-regulated by LPS treatment in a time-dependent manner in primary blood monocytes and polymorphonuclear neutrophils. A reduction was also observed in RAW264 and differentiated HL-60 cells. Notably, exogenous introduction of the dominant negative form of TLR4 and siRNA of p38 resulted in inhibition of LPS-induced SIGIRR down-regulation, whereas treatment with p38 activator anisomycin showed a dose-dependent decrease in SIGIRR expression, suggesting TLR4-p38 signal as a critical pathway for LPS-induced SIGIRR down-regulation. Finally, reporter gene and chromatin immunoprecipitation assays demonstrated that Sp1 is a key factor that directly binds to the proximal promoter of SIGIRR gene and consequently regulates basal SIGIRR expression, which is negatively regulated by the LPS-dependent TLR4-p38 pathway. In summary, the data precisely demonstrate how LPS down-regulates SIGIRR expression and provide a role of LPS signal that counteracts Sp1-dependent basal promoter activation of SIGIRR gene via TLR4-p38 pathway in non-epithelial innate immune cells.
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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.