IL1B

The protein encoded by this gene is a member of the interleukin 1 cytokine family. This cytokine is produced by activated macrophages as a proprotein, which is proteolytically processed to its active form by caspase 1 (CASP1/ICE). This cytokine is an important mediator of the inflammatory response, and is involved in a variety of cellular activities, including cell proliferation, differentiation, and apoptosis. The induction of cyclooxygenase-2 (PTGS2/COX2) by this cytokine in the central nervous system (CNS) is found to contribute to inflammatory pain hypersensitivity. This gene and eight other interleukin 1 family genes form a cytokine gene cluster on chromosome 2. [provided by RefSeq, Jul 2008]

Interleukin 1 Beta

Potent proinflammatory cytokine. Initially discovered as the major endogenous pyrogen, induces prostaglandin synthesis, neutrophil influx and activation, T-cell activation and cytokine production, B-cell activation and antibody production, and fibroblast proliferation and collagen production. Promotes Th17 differentiation of T-cells. Synergizes with IL12/interleukin-12 to induce IFNG synthesis from T-helper 1 (Th1) cells (PubMed:10653850).

Plays a role in angiogenesis by inducing VEGF production synergistically with TNF and IL6 (PubMed:12794819).

Activation of MAPK activity Source: BHF-UCL
Apoptotic process Source: ProtInc
Cell-cell signaling Source: ProtInc
Cellular response to drug Source: MGI
Cellular response to lipopolysaccharide Source: GO_Central
Cellular response to mechanical stimulus Source: UniProtKB
Cellular response to organic cyclic compound Source: UniProtKB
Cellular response to organic substance Source: MGI
Cytokine-mediated signaling pathway Source: BHF-UCL
Embryo implantation Source: BHF-UCL
Fever generation Source: UniProtKB-KW
Hyaluronan biosynthetic process Source: UniProtKB
Immune response Source: InterPro
Inflammatory response Source: UniProtKB
Interleukin-1-mediated signaling pathway Source: BHF-UCL
Lipopolysaccharide-mediated signaling pathway Source: UniProtKB
MAPK cascade Source: UniProtKB
Monocyte aggregation Source: UniProtKB
Negative regulation of adiponectin secretion Source: BHF-UCL
Negative regulation of cell population proliferation Source: BHF-UCL
Negative regulation of extrinsic apoptotic signaling pathway in absence of ligand Source: BHF-UCL
Negative regulation of gap junction assembly Source: ARUK-UCL
Negative regulation of glucose transmembrane transport Source: BHF-UCL
Negative regulation of insulin receptor signaling pathway Source: BHF-UCL
Negative regulation of lipid catabolic process Source: BHF-UCL
Negative regulation of lipid metabolic process Source: BHF-UCL
Negative regulation of MAP kinase activity Source: BHF-UCL
Negative regulation of neurogenesis Source: ARUK-UCL
Negative regulation of synaptic transmission Source: ARUK-UCL
Positive regulation of angiogenesis Source: BHF-UCL
Positive regulation of calcidiol 1-monooxygenase activity Source: BHF-UCL
Positive regulation of cell adhesion molecule production Source: BHF-UCL
Positive regulation of cell division Source: UniProtKB-KW
Positive regulation of cell migration Source: BHF-UCL
Positive regulation of cell population proliferation Source: BHF-UCL
Positive regulation of complement activation Source: ARUK-UCL
Positive regulation of DNA-binding transcription factor activity Source: BHF-UCL
Positive regulation of epithelial to mesenchymal transition Source: BHF-UCL
Positive regulation of fever generation Source: BHF-UCL
Positive regulation of gene expression Source: UniProtKB
Positive regulation of glial cell proliferation Source: ARUK-UCL
Positive regulation of granulocyte macrophage colony-stimulating factor production Source: BHF-UCL
Positive regulation of heterotypic cell-cell adhesion Source: UniProtKB
Positive regulation of histone acetylation Source: BHF-UCL
Positive regulation of histone phosphorylation Source: BHF-UCL
Positive regulation of immature T cell proliferation in thymus Source: GO_Central
Positive regulation of inflammatory response Source: ARUK-UCL
Positive regulation of interferon-gamma production Source: UniProtKB
Positive regulation of interleukin-2 production Source: BHF-UCL
Positive regulation of interleukin-6 production Source: ARUK-UCL
Positive regulation of interleukin-8 production Source: UniProtKB
Positive regulation of JNK cascade Source: ARUK-UCL
Positive regulation of lipid catabolic process Source: BHF-UCL
Positive regulation of membrane protein ectodomain proteolysis Source: BHF-UCL
Positive regulation of mitotic nuclear division Source: BHF-UCL
Positive regulation of monocyte chemotactic protein-1 production Source: UniProtKB
Positive regulation of myosin light chain kinase activity Source: BHF-UCL
Positive regulation of neuroinflammatory response Source: ARUK-UCL
Positive regulation of NF-kappaB transcription factor activity Source: BHF-UCL
Positive regulation of NIK/NF-kappaB signaling Source: BHF-UCL
Positive regulation of nitric oxide biosynthetic process Source: BHF-UCL
Positive regulation of p38MAPK cascade Source: ARUK-UCL
Positive regulation of phagocytosis Source: AgBase
Positive regulation of prostaglandin biosynthetic process Source: ARUK-UCL
Positive regulation of prostaglandin secretion Source: BHF-UCL
Positive regulation of protein export from nucleus Source: BHF-UCL
Positive regulation of protein phosphorylation Source: BHF-UCL
Positive regulation of RNA biosynthetic process Source: ARUK-UCL
Positive regulation of T cell mediated immunity Source: BHF-UCL
Positive regulation of T cell proliferation Source: BHF-UCL
Positive regulation of T-helper 1 cell cytokine production Source: UniProtKB
Positive regulation of transcription, DNA-templated Source: UniProtKB
Positive regulation of vascular endothelial growth factor production Source: BHF-UCL
Positive regulation of vascular endothelial growth factor receptor signaling pathway Source: BHF-UCL
Protein kinase B signaling Source: UniProtKB
Purinergic nucleotide receptor signaling pathway Source: Reactome
Regulation of ERK1 and ERK2 cascade Source: BHF-UCL
Regulation of establishment of endothelial barrier Source: UniProtKB
Regulation of I-kappaB kinase/NF-kappaB signaling Source: BHF-UCL
Regulation of insulin secretion Source: BHF-UCL
Regulation of neurogenesis Source: ARUK-UCL
Regulation of nitric-oxide synthase activity Source: UniProtKB
Response to interleukin-1 Source: ARUK-UCL
Response to lipopolysaccharide Source: ARUK-UCL
Sequestering of triglyceride Source: BHF-UCL
Signal transduction Source: ProtInc
Smooth muscle adaptation Source: BHF-UCL
Vascular endothelial growth factor production Source: UniProtKB

Cytosol; Extracellular exosome; Secreted; Lysosome. The precursor is cytosolic. In response to inflammasome-activating signals, such as ATP for NLRP3 inflammasome or bacterial flagellin for NLRC4 inflammasome, cleaved and secreted. IL1B lacks any known signal sequence and the pathway(s) of its secretion is(are) not yet fully understood (PubMed:24201029). On the basis of experimental results, several unconventional secretion mechanisms have been proposed. 1. Secretion via secretory lysosomes: a fraction of CASP1 and IL1B precursor may be incorporated, by a yet undefined mechanism, into secretory lysosomes that undergo Ca2+-dependent exocytosis with release of mature IL1B (PubMed:15192144). 2. Secretory autophagy: IL1B-containing autophagosomes may fuse with endosomes or multivesicular bodies (MVBs) and then merge with the plasma membrane releasing soluble IL1B or IL1B-containing exosomes (PubMed:24201029). However, autophagy impacts IL1B production at several levels and its role in secretion is still controversial. 3. Secretion via exosomes: ATP-activation of P2RX7 leads to the formation of MVBs containing exosomes with entrapped IL1B, CASP1 and other inflammasome components. These MVBs undergo exocytosis with the release of exosomes. The release of soluble IL1B occurs after the lysis of exosome membranes (By similarity). 4. Secretion by microvesicle shedding: activation of the ATP receptor P2RX7 may induce an immediate shedding of membrane-derived microvesicles containing IL1B and possibly inflammasome components. The cytokine is then released in the extracellular compartment after microvesicle lysis (PubMed:11728343). 5. Release by translocation through permeabilized plasma membrane. This may occur in cells undergoing pyroptosis due to sustained activation of the inflammasome (By similarity). 6. The secretion is dependent on protein unfolding and facilitated by the cargo receptor TMED10; it results in the protein translocation from the cytoplasm into the ERGIC (endoplasmic reticulum-Golgi intermediate compartment) followed by vesicle entry and secretion, and enhanced by chaperones HSP90AB1 and HSP90B1/GRP9 (PubMed:32272059). These mechanisms may not be mutually exclusive.

Secreted; Cytoplasm. The lack of a specific hydrophobic segment in the precursor sequence suggests that IL-1 is released by damaged cells or is secreted by a mechanism differing from that used for other secretory proteins. The secretion is dependent on protein unfolding and facilitated by the cargo receptor TMED10; it results in protein translocation from the cytoplasm into the ERGIC (endoplasmic reticulum-Golgi intermediate compartment) followed by vesicle entry and secretion (PubMed:32272059).

Activation of the IL1B precursor involves a CASP1-catalyzed proteolytic cleavage. Processing and secretion are temporarily associated.