IL-18 Responsive Luciferase Reporter HEK293 Cell Line

The IL-18 Responsive Luciferase Reporter HEK293 Cell Line is a HEK293 cell line engineered to express both human IL-18R1 (interleukin-18 receptor 1) (NM_003855.5) and human IL18RAP (Interleukin 18 receptor accessory protein) (NM_003853.3) separated by a self-cleaving P2A peptide. The construct was delivered by lentiviral transduction of NF-kappaB Luciferase Reporter HEK293 Cell Line (#60650), which expresses a firefly luciferase reporter driven by NFkappaB (nuclear factor Kappa B) response elements located upstream of the minimal TATA promoter. After activation by IL-18, the endogenous transcription factor NF-kappaB binds to the response elements, inducing transcription of the luciferase reporter. This cell line has been validated to respond to IL-18 and to IL-18 targeting antibodies. Figure 1: Illustration of the mechanism of reporter activation in IL-18 Luciferase Reporter HEK293 Cell Line. Interested in having us perform the screening and profiling of inhibitors or blocking antibodies? Visit our Cell Signaling Pathway Screening. Interleukin 18 is a pro-inflammatory cytokine belonging to the IL-1 superfamily of cytokines and plays an important role as a modulator of both innate and adaptive immunity. The inactive precursor form of IL-18 (pro-IL-18) is constitutively expressed in the cytoplasm of both hematopoietic and non-hematopoietic cells including macrophages, dendritic cells, keratinocytes, and epithelial cells. IL-18 signaling is initiated via inflammasome mediated activation of caspase-1 which cleaves the precursor to produce active IL-18. Mature IL-18 binds to the IL-18 alpha chain (IL-18Ralpha) and IL-18 receptor beta chain (IL-18Rbeta, also known as IL-18RAP) to form a high affinity signaling complex that activates downstream signaling pathways including NF-kappaB (nuclear factor Kappa B) and MAPK (mitogen activated protein kinase). In the presence of IL-12 or IL-15, IL-18 drives Th1 responses by signaling to T cells and NK cells to induce IFNgamma (interferon gamma) production, which is essential for immune responses to infections. Additionally, IL-18 upregulates the expression of genes critical for cell survival/differentiation such as TNF (tumor necrosis factor) and FasL (Fas ligand) for cell death. Therapeutic strategies designed to neutralize excess IL-18 is a growing field of research showing promising results for the treatment of autoinflammatory diseases. GSK-1070806 (Aletekitug) is a monoclonal antibody that neutralizes IL-18 to treat atopic dermatitis (AD). Additional therapies include Tadekinig alfa, which is a recombinant IL-18 binding protein that inhibits free IL-18 and was developed for the treatment of NLRC4-MAS (NLR family caspase activation and recruitment domain-containing 4 Macrophage Activation Syndrome) and XIAP (X-linked inhibitor of apoptosis protein) deficiency.