IL18
GeneName
IL18
Summary
IL18, also known as interleukin 18, is a 22 kDa pro-inflammatory cytokine that is primarily secreted into the extracellular space and is expressed in various tissues, including immune cells. It plays a pivotal role in immune response and inflammation by promoting the activation and proliferation of natural killer (NK) cells and T-helper 1 (Th1) cells. IL18 exerts its effects through binding to the interleukin-18 receptor, triggering multiple signalling pathways that lead to the production of other cytokines and chemokines. This cytokine is involved in various biological processes, including angiogenesis, defense against pathogens, and the regulation of inflammatory responses, making it a key player in both innate and adaptive immunity.
Importance
IL18 is relevant to: - The regulation of immune responses, particularly in the context of infections and autoimmune diseases due to its role in NK cell activation and Th1 differentiation. - Inflammatory disorders, as it contributes to the pathogenesis of conditions such as rheumatoid arthritis and inflammatory bowel disease. - Cancer immunotherapy, where its ability to enhance anti-tumour immunity is being explored for therapeutic strategies. - Metabolic diseases, given its involvement in cholesterol homeostasis and triglyceride regulation.
Top Products
For researchers investigating IL18, we highly recommend the top-selling recombinant antibody, Anti-IL-18 antibody [EPR19954-188] (ab243091). This antibody has been validated in knockout models, ensuring reliable performance in your experiments. It is suitable for a variety of applications, including Western blotting (WB), immunohistochemistry (IHC), and flow cytometry (FC), making it a versatile choice for your research needs. With 43 citations, this antibody is gaining recognition in the scientific community for its effectiveness in IL18 detection. The Human IL-18 Matched Antibody Pair Kit (ab218185) is a reliable option for researchers looking to measure IL-18 in their experiments.
Abcam Product Citation Summary
The data indicates that IL18 is being studied in various contexts related to inflammation, apoptosis, and pyroptosis. The use of human RPE and HeLa cells highlights its relevance in human cellular responses, while the study involving YAMC cells infected with Salmonella suggests its role in the immune response.
Abcam Product Citation Table
Function
Pro-inflammatory cytokine primarily involved in epithelial barrier repair, polarized T-helper 1 (Th1) cell and natural killer (NK) cell immune responses (PubMed:10653850). Upon binding to IL18R1 and IL18RAP, forms a signaling ternary complex which activates NF-kappa-B, triggering synthesis of inflammatory mediators (PubMed:14528293, PubMed:25500532, PubMed:37993714). Synergizes with IL12/interleukin-12 to induce IFNG synthesis from T-helper 1 (Th1) cells and natural killer (NK) cells (PubMed:10653850). Involved in transduction of inflammation downstream of pyroptosis: its mature form is specifically released in the extracellular milieu by passing through the gasdermin-D (GSDMD) pore (PubMed:33883744).
Post-translational modifications
The pro-IL-18 precursor is processed by CASP1, CASP4 or CASP5 to yield its mature, active form (PubMed:15326478, PubMed:25261253, PubMed:37993712, PubMed:37993714, PubMed:9334240). The pro-IL-18 precursor features autoinhibitory interactions between the propeptide and the post-cleavage-site region, preventing recognition by the IL18R1 receptor (PubMed:37993714). Processing by CASP1, CASP4 or CASP5 induces conformational changes to generate critical receptor-binding sites (PubMed:37993714). The mature form is then secreted and released in the extracellular milieu by passing through the gasdermin-D (GSDMD) pore (PubMed:33883744, PubMed:37993714). In contrast, cleavage by CASP3 inactivates IL18 (PubMed:37993714, PubMed:9334240).
Sequence Similarities
Belongs to the IL-1 family.
Tissue Specificity
Isoform 2
Expressed in ovarian carcinoma but undetectable in normal ovarian epithelial cells. Resistant to proteolytic activation by caspase-1 and -4.
Cellular localization
- Cytoplasm
- Cytosol
- Secreted
- The precursor is cytosolic (PubMed:33883744). In response to inflammasome-activating signals, cleaved and secreted (PubMed:33883744, PubMed:37993712, PubMed:37993714). Mature form is secreted and released in the extracellular milieu by passing through the gasdermin-D (GSDMD) pore (PubMed:33883744, PubMed:37993714). In contrast, the precursor form is not released, due to the presence of an acidic region that is proteolytically removed by CASP1, CASP4 or CASP5 during maturation (PubMed:33883744, PubMed:37993714). The secretion is dependent on protein unfolding and facilitated by the cargo receptor TMED10 (PubMed:32272059).
Alternative names
IGIF, IL1F4, IL18, Interleukin-18, IL-18, Iboctadekin, Interferon gamma-inducing factor, Interleukin-1 gamma, IFN-gamma-inducing factor, IL-1 gamma
Database links
swissprot:Q14116 entrezGene:3606 omim:600953
Other research areas
- Immuno-oncology