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Immediate Cytokine Responses to Endotoxin: Tumor Necrosis Factor-α and the lnterleukin-1 Family
Published in Helmut Brade, Steven M. Opal, Stefanie N. Vogel, David C. Morrison, Endotoxin in Health and Disease, 2020
The IL-1 family members are presently IL-1β, IL-1α, and IL-lRa. They are considered a family primarily because they bind to the same receptor (the IL-1 receptor type I, IL-1RI). They also bind to the IL-1R type II decoy receptor (albeit with quite different affinities compared to the IL-1RI). The IL-1 receptor signaling complex is comprised of the IL-1 ligand binding IL-1RI and the IL-1R accessory protein (IL-lR-AcP), similar to the IL-2 receptor complex in which the p55 ligand binding IL-2Rα forms a complex with the p75 IL-2Rβ. Although the three IL-1 cytokines share less than 30% primary amino acid sequence homologies, they are structurally very similar since each is an all-β-pleated, barrel-like form. In that regard, two other cytokines have all-β-pleated forms: acidic fibroblast growth factor and IL-18. Fibroblast growth factor is not part of the IL-1 family because this growth factor does not bind to IL-1 receptors. However, recent studies suggest that IL-18 may now have to be considered part of the IL-1 family. This is based on the finding that IL-18 is the natural ligand for the IL-1 receptor family member called IL-lR-related protein (IL-1Rrp) (57).
Cytokines
Published in Peter Kam, Ian Power, Michael J. Cousins, Philip J. Siddal, Principles of Physiology for the Anaesthetist, 2020
Peter Kam, Ian Power, Michael J. Cousins, Philip J. Siddal
Interleukins stimulate the proliferation of T-helper and cytotoxic cells and B lymphocytes. IL-1 is secreted by macrophages as two polypeptides, IL-1α and IL-1β. Both IL-1α and IL-1β activate T and B lymphocytes, macrophages and endothelium and increase production of acute-phase proteins. IL-1 releases prostaglandins in the anterior hypothalamus (causing fever) and endorphins in the brain (attenuation of pain after injury).
Interleukins and Metalloproteinases in Arthritis
Published in Thomas F. Kresina, Monoclonal Antibodies, Cytokines, and Arthritis, 2020
Synergy and more profound biologic activities are observed with combination treatments (IL-1 and IL-6; acute-phase proteins; IL-1 and tumor necrosis factor, TNF; thymocyte proliferation) (32,53–57). In addition, several monokines induce similar biologic activities and/or induce the release of other monokines. One of the more interesting monokines associated with many of the characteristics of arthritis and inflammation is IL-1. The cloning of IL-1 genes and the purification of IL-1 reveal that there are two major classes of IL-1 protein, designated IL-1α and IL-1β. The cloning and expression of the cDNA for human IL-1α and IL-1β also reveals that these proteins are synthesized as a precursor molecule and that the mature forms of the protein are located in the carboxyl terminus of the precursor (32,58,59).
Immune suppressive function of IL-1α release in the tumor microenvironment regulated by calpain 1
Published in OncoImmunology, 2022
Dandan Lin, Yu Mei, Lei Lei, Zuhairah Binte Hanafi, Ziqi Jin, Yonghao Liu, Yuan Song, Yinsheng Zhang, Bo Hu, Chunliang Liu, Jinhua Lu, Haiyan Liu
IL-1α is an important cytokine in IL-1 family, and it is constitutively expressed in a variety of cells. Upon environmental stimulation, both hematopoietic and non-hematopoietic cells can secret IL-1α to promote inflammation.1 IL-1α is translated into 31 kDa precursor form (pro-IL-1α). Pro-IL-1α has a functional nuclear localization sequence (NLS) in the N-terminal domain for nuclear translocation, which is retained in the propiece (N-terminal cleavage product) of IL-1α after the cleavage by calpains or other proteases.2 Pro-IL-1α and IL-1α-propiece can both translocate to the nucleus and bind to the chromatin to exert many functions, such as DNA damage repair, cell growth, differentiation, and adhesion.3,4 Pro-IL-1α is myristoylated and then anchors to the cell membrane via a lectin-like interaction.5 Membrane IL-1α is bioactive through IL-1 receptor signaling pathway and is found to promote anti-tumor immune response.6 The pro-IL-1α can also be cleaved to generate the secreted mature form (17 kDa).7 IL-1α secretion is rarely detected in healthy human body fluids.8 However, pro-IL-1α and mature IL-1α are thought to be released from necrotic cells to initiate inflammation.9 Therefore, IL-1α is a dual function cytokine that exerts its function intracellularly and also binds to its cell membrane receptor to perform extracellular functions.
Human oncogenic viruses: an overview of protein biomarkers in viral cancers and their potential use in clinics
Published in Expert Review of Anticancer Therapy, 2022
ANXA2 can be found in plasma, saliva and urine. CHI3L1, EPHA4, and SDC1 can be found in plasma and another body fluid. In addition, both ALDH1A1 and IL1A can be found in serum, urine, and saliva, respectively. CDK1, GSK3B, MCM2, PARP1 and UBE2I can be found in plasma and TOP2A in urine (Figure 2(a)). Palbociclib is an approved drug target for CCND1. Bosutinib and dasatinib are approved drug targets for EPHA4 and EPHA5, respectively. GSK3B has 2 approved drug targets (lithium carbonate and lithium citrate). A drug called rilonacept is a target for IL1A. PARP1 has 4 drug targets as follows; olaparib, niraparib, rucaparib and talazoparib tosylate (Figure 2(b)). According to the ultimate protein biomarkers, ALDH1A1, CDK1, ETS1 and NCOA3 have oncoprotein properties while GSK3B has tumor suppressor properties (Figure 3(a)). The biomarkers such as CDK1, E2F4, KAT2B and UBE2I have interactions with highly oncogenic HPV proteins (Figure 3(c); Table S2).
Effects of stem cell-derived exosomes on neuronal apoptosis and inflammatory cytokines in rats with cerebral ischemia-reperfusion injury via PI3K/AKT pathway-mediated mitochondrial apoptosis
Published in Immunopharmacology and Immunotoxicology, 2021
Ying Zhang, Jun Yu, Jing Liu, Hongbiao Liu, Jing Li
IL-1α is produced by monocytes, endothelial cells, and fibroblasts and plays a central role in regulating immune responses and tissue repair [30]. IL-2 also plays a crucial role in the immune response and promotes Th0 and antibody responses. TNF-α is an inflammatory mediator that inhibits viral replication and eliminates virus-infected cells. Its expression level can reflect the severity of disease and inflammatory state. Furthermore, IFN-γ is a free radical dimer cytokine that is mainly produced by activated T-cells, natural killer cells, and NK cells and could induce inflammation and antiviral response. IL-1α, IL-2, and TNF-α were present at low concentrations in healthy rats, whereas IFN-γ was in dynamic equilibrium. In rats with cerebral ischemia-reperfusion injury, IL-1α, IL-2, and TNF-α levels increase and IFN-γ levels decrease [13]. In this study, the levels of IL-1α, IL-2, and TNF-α in the SC-Exos group were lower than those in the model group, whereas the levels of IFN-γ were higher in the SC-Exos group than in the model group, indicating that SC-Exos can ameliorate the abnormal inflammatory cytokine levels caused by cerebral ischemia-reperfusion injury.