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Interleukin-1B (Gene IL1B) Homo sapiensIL-1alpha (IL1-F1), IL-1 beta (IL1-F2) and IL-1ra (IRAP, IL1-F3)) are the original members of the interleukin-1 family which has grown to 11 members including IL1-F4 (IL-18, IGIF), IL1-F5 (delta), IL1-F6 (epsilon), IL1-F7 (zeta), IL1-F8 (eta), IL1-F9, IL1-F10 (theta), and IL-F11 (IL-33). The IL-1beta gene (map locus Entrez, 2q14; Ensembl, 2q13; HGNC, 2q13-q21) product, pro-IL-1beta, is a 269 (30.7 kDa) amino acids long precursor peptide which is processed into a 153 (17 kDa) amino acids long mature cytokine, IL-1beta, by removal of a 116 amino acid N-terminal peptide, the propiece. IL-1beta is active only in its mature processed form, whereas IL-1alpha is active in both its precursor and mature forms, Dinarello CA, (1994, 1996). Acting as cytokines, IL-1beta and IL-1alpha propagate virtually identical signals via IL-1R1 binding. IL-1beta is normally secreted giving it access to the IL-1R1 receptor, whereas IL-1alpha is predominantly intracellular, unless the cell is damaged. IL-1beta signal initiation and transduction requires the occupation of only a few IL-1R1 receptors. IL-1beta is a potent pyrogen whose activity is tightly regulated. The transcription of IL-1beta is induced by a wide array of factors involved with a variety of challenges to the cell. These include: infection by microbes; stress by hyperosmolarity, hypoxia, ischemia, or radiation damage; inflammation inducing agents, urate and calcium pyrophosphate crystals or advanced glycosylated end-products (AGE); oxidized lipids such as LDL; and a variety of cytokines and growth factors such as IL-1, TNF, IL-2, IL-3, IL12, GM-CSF, M-CSF, SCF or PDGF. These factors sustain an elevated level of IL-1beta mRNA that is translated when the cell experiences further stimulation with IL-1 or bacterial endotoxins, lipopolysaccharides (LPS). Once pro-IL-1beta is produced, it remains essentially inactive in the cytoplasm until it is cleaved by interleukin 1 beta converting enzyme (ICE) and secreted into the extracellular space or circulation. The cleavage of pro-IL-1beta by ICE into an active molecule is a physiologically controlled event: however, under conditions of cell necrosis or mechanical injury other enzymes such trypsin, elastase, chymotrypsin, mast cell chymase and various proteases can cleave and activate IL-1beta. Extracellular IL-1beta must compete with IL-1Ra, which binds to IL-1R1 but sends no signal and avoid dead-end binding to soluble IL-1R1 or IL-1RII. IL-1beta binding to the IL-1R1 receptor is not sufficient to propagate a signal. This complex must associate with another regulated molecule, IL-1R accessory protein (IL-1R-AcP). The IL-1beta:IL-1R1:IL-1R-AcP complex initiates the cell signaling pathways. IL-1beta is a multifunctional molecule that effects the transcription of a long list of genes that affect major processes such as inflammation, immunity and hemopoiesis. It regulates pro-inflammatory and proliferative cytokines and growth factors, chemokines and adhesion molecules and facilitates immune defense against infections. Three important inflammatory genes that are upregulated by IL-1 are induced nitric oxide synthase (iNOS), Pfeilschifter J et al. (1990, 1992), Eberhardt W, et al. (1998), Kilyada AY, et al. (2001); type-2 cyclooxygenase (COX-2), Croxtal JD, et al. (1996), Beasly D et al. (1999) and phospholipase-A2 (PLA2), Newman SP, et al. (1997). IL-1 activity is involved with a large number of disease conditions including infections, cancers, trauma, ischemia, asthma, GVHD and inflammations with a common denominator that these diseases involve some level of cell damage or necrosis. Il-1beta has been linked to increased tumor invasiveness, angiogenesis and immune suppression in cancer cells, Song X, et al. (2003); Apte RN et al. (2006). The importance of IL-1 is illustrated by the fact that the search entry "IL-1" generates over 132,000 PubMed hits. Sigma offers antibodies and shRNAs useful for the study of Interleukin-1B gene products. References: Apte RN, et al. (2006) The involvement of IL-1 in tumorigenesis, tumor invasiveness, metastasis and tumor-host interactions. Cancer Metastasis Rev. 25: 387-408. |
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