title: Interleukin-1α.
abstract: Although the IL-1α molecule has long been recognized, information about its distinct role in various diseases is limited, since most clinical studies have focused on the role of IL-1β. Despite triggering the same IL-1 receptor as does IL-1β, there is, however, a distinct role for IL-1α in some inflammatory diseases. IL-1α is a unique cytokine since it is constitutively present intracellularly in nearly all resting non-hematopoietic cells in health as well as being up-regulated during hypoxia. During cell necrosis, IL-1α functions as an alarm molecule and thus plays a critical role early in inflammation. Following its release from damage tissue cells, IL-1α mediates neutrophil recruitment to the site of injury, inducing IL-1β, other cytokines and chemokines from surrounding resident cells. Another unique attribute of IL-1α is its nuclear localization sequence present in the N-terminal half of the precursor termed the propiece. The IL-1α propiece translocates into the nucleus and participates in the regulation of transcription. Therefore, IL-1α, like IL-1 family members IL-33 and IL-37, is a 'dual-function' cytokine binding to chromatin as well as to its cell surface receptor. Some cancer cells can express membrane IL-1α, which can increase immunogenicity of tumor cells and serve in anti-tumor immune surveillance and tumor regression. However, in the tumor microenvironment, precursor IL-1α released from dying tumor cells is inflammatory and, similar to IL-1β, increases tumor invasiveness and angiogenesis.
authors.affiliation: Faculty of Health Sciences, Department of Clinical Biochemistry and Pharmacology, Ben-Gurion University of the Negev, Beer-Sheva, Israel. Electronic address: riderp@gmail.com.
authors.forename: Peleg
authors.initials: P
authors.lastname: Rider
authors.affiliation: School of Medicine, Department of Pathology, Stanford University, Palo Alto, CA, USA.
authors.forename: Yaron
authors.initials: Y
authors.lastname: Carmi
authors.affiliation: The Shraga Segal Department of Microbiology, Immunology and Genetics and The Cancer Research Center, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel.
authors.forename: Elena
authors.initials: E
authors.lastname: Voronov
authors.affiliation: The Shraga Segal Department of Microbiology, Immunology and Genetics and The Cancer Research Center, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel.
authors.forename: Ron N
authors.initials: RN
authors.lastname: Apte
mesh_terms: D000818:Animals; D015687:Cell Hypoxia / Q000276:immunology; D002471:Cell Transformation, Neoplastic / Q000473:pathology; D002843:Chromatin; D006801:Humans; D007249:Inflammation / Q000276:immunology*; D053582:Interleukin-1alpha / Q000235:genetics / Q000276:immunology*; D051379:Mice; D009336:Necrosis / Q000473:pathology; D009361:Neoplasm Invasiveness / Q000473:pathology; D009369:Neoplasms / Q000276:immunology; D020556:Neutrophil Infiltration / Q000276:immunology; D017472:Receptors, Interleukin-1 / Q000276:immunology
chemical_list: D002843:Chromatin; D053582:Interleukin-1alpha; D017472:Receptors, Interleukin-1