IL18

The protein encoded by this gene is a proinflammatory cytokine that augments natural killer cell activity in spleen cells, and stimulates interferon gamma production in T-helper type I cells. Alternatively spliced transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Aug 2011]

Interleukin 18

Proinflammatory 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).

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).

Activation of protein kinase B activity Source: BHF-UCL
Angiogenesis Source: UniProtKB
Cell-cell signaling Source: ProtInc
Cell population proliferation Source: Ensembl
Cellular response to organic cyclic compound Source: UniProtKB
Cholesterol homeostasis Source: BHF-UCL
Inflammatory response Source: UniProtKB
Interleukin-18-mediated signaling pathway Source: UniProtKB
Lipopolysaccharide-mediated signaling pathway Source: UniProtKB
MAPK cascade Source: UniProtKB
Natural killer cell activation Source: Ensembl
Natural killer cell mediated cytotoxicity Source: Ensembl
Negative regulation of myoblast differentiation Source: Ensembl
Neutrophil activation Source: Ensembl
Positive regulation of activated T cell proliferation Source: UniProtKB
Positive regulation of chemokine production Source: UniProtKB
Positive regulation of cold-induced thermogenesis Source: YuBioLab
Positive regulation of granulocyte macrophage colony-stimulating factor production Source: BHF-UCL
Positive regulation of inflammatory response Source: BHF-UCL
Positive regulation of interferon-gamma production Source: UniProtKB
Positive regulation of interleukin-13 production Source: UniProtKB
Positive regulation of interleukin-17 production Source: BHF-UCL
Positive regulation of macrophage derived foam cell differentiation Source: BHF-UCL
Positive regulation of natural killer cell proliferation Source: BHF-UCL
Positive regulation of neuroinflammatory response Source: ARUK-UCL
Positive regulation of NF-kappaB transcription factor activity Source: UniProtKB
Positive regulation of NIK/NF-kappaB signaling Source: Ensembl
Positive regulation of NK T cell proliferation Source: BHF-UCL
Positive regulation of phosphatidylinositol 3-kinase signaling Source: BHF-UCL
Positive regulation of protein kinase B signaling Source: BHF-UCL
Positive regulation of smooth muscle cell proliferation Source: BHF-UCL
Positive regulation of T-helper 1 cell cytokine production Source: UniProtKB
Positive regulation of T-helper 2 cell differentiation Source: BHF-UCL
Positive regulation of tissue remodeling Source: BHF-UCL
Positive regulation of transcription by RNA polymerase II Source: BHF-UCL
Positive regulation of tyrosine phosphorylation of STAT protein Source: CACAO
Regulation of cell adhesion Source: UniProtKB
Sleep Source: UniProtKB
T-helper 1 type immune response Source: UniProtKB
Triglyceride homeostasis Source: BHF-UCL
Type 2 immune response Source: UniProtKB

Cytoplasm; Secreted. The precursor is cytosolic (PubMed:33883744). In response to inflammasome-activating signals, cleaved and secreted (PubMed:33883744). Mature form is secreted and released in the extracellular milieu by passing through the gasdermin-D (GSDMD) pore (PubMed:33883744). In contrast, the precursor form is not released, due to the presence of an acidic region that is proteolytically removed by CASP1 during maturation (PubMed:33883744). The secretion is dependent on protein unfolding and facilitated by the cargo receptor TMED10 (PubMed:32272059).

The pro-IL-18 precursor is processed by CASP1 or CASP4 to yield the active form.