Interleukin 1 beta
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Location (UCSC) | Chr 2: 112.83 – 112.84 Mb | Chr 2: 129.21 – 129.21 Mb | |||||||
PubMed search | [3] | [4] |
View/Edit Human | View/Edit Mouse |
Interleukin-1 beta (IL-1β) also known as leukocytic pyrogen, leukocytic endogenous mediator, mononuclear cell factor, lymphocyte activating factor and other names, is a
Function
The fever-producing property of human leukocytic
IL-1β is a member of the
IL-1β, in combination with
Different
Properties
Before cleavage by caspase 1, pro-IL-1β has a molecular weight of 37 kDa.[13] The molecular weight of the proteolytically processed IL-1β is 17.5 kDa. IL-1β has the following amino acid sequence:
- APVRSLNCTL RDSQQKSLVM SGPYELKALH LQGQDMEQQV VFSMSFVQGE ESNDKIPVAL GLKEKNLYLS CVLKDDKPTL QLESVDPKNY PKKKMEKRFV FNKIEINNKL EFESAQFPNW YISTSQAENM PVFLGGTKGG QDITDFTMQF VSS
The physiological activity determined from the dose dependent proliferation of murine D10S cells is 2.5 x 108 to 7.1 x 108 units/mg.
IL-1β is present in other species of animals, however non-mammalian sequences of IL-1β lack a conserved cascase-1 cleavage site.[17][18][19]
Clinical significance
Increased production of IL-1β causes a number of different
Intestinal dysbiosis has been observed to induce osteomyelitis through a IL-1β dependent manner.[21]
The presence of IL-1β has been also found in patients with multiple sclerosis (a chronic autoimmune disease of the central nervous system). However, it is not known exactly which cells produce IL-1β. Treatment of multiple sclerosis with glatiramer acetate or natalizumab has also been shown to reduce the presence of IL-1β or its receptor.[22]
Role in carcinogenesis
Several types of inflammasomes are suggested to play role in tumorgenesis due to their immunomodulatory properties, modulation of gut microbiota, differentiation and apoptosis. Over-expression of IL-1β caused by inflammasome may result in carcinogenesis. Some data suggest that
Furthermore, it has been found that in breast cancer cells, IL-1β activates p38 and p42/22 MAPK pathways which ultimately lead to the secretion of the RANK/RANKL inhibitor osteoprotegerin. Higher osteoprotegerin and IL-1β levels are a characteristic of breast cancer cells with a higher metastatic potential.[25]
In HIV-1 infections
The human immunodeficiency virus (HIV) infects cells of the immune system, such as macrophages, dendritic cells, and CD4+ T helper cells (TH). The latter can be infected by the virus in various ways with different fates depending on the state of activation of the T helper cell.[13]
Firstly, TH cells can die of viral lysis due to an active infection that produces enough virions to kill the cell. Secondly, CD4+ T cells can be infected by the virus but instead of producing more viral particles, the cell enters a latent phase. In this period, the T helper cells looks identical from the outside but any stressor could lead to the renewed production of HIV and its propagation to new immune cells. Lastly, the TH cell can become abortively infected, where the virus gets detected inside the cell and a programmed cell-death, known as pyroptosis, kills the infected cell. Pyroptosis is mediated via caspase-1 and is characterized by cell lysis and the secretion of IL-1β causing inflammation and attraction of more immune cells. This can create a cycle of CD4+ T cells getting abortively infect with HIV, dying of pyroptosis, new T helper cells arriving to the site of inflammation where they get infected again. The results is the depletion of T helper cells. Even though, levels of IL-1β in blood are not majorly different between HIV positive and negative individuals, studies have shown elevated levels of IL-1β of lymphatic tissue in HIV-infected individuals.[13]
In fact, the gut-associated lymphoid tissue (GALT) has a high density of immune cells as the gut is an interface between symbiotic gut microbes that should remain with the host and pathogenic bacteria that should not gain access into the circulatory system. If HIV-infection leads to the secretion of IL-1βin monocytes and macrophages, it causes inflammation of this area. The mucosal epithelial layer responds to this by producing less or altering the tight junction proteins which makes it easier for pathogenic microbes to move into the lamina propria. Here, the pathogens can further activate local immune cells and amplify the inflammatory response.[13]
Retinal degeneration
It has been shown that IL-1 family plays important role in inflammation in many degenerative diseases, such as age-related macular degeneration, diabetic retinopathy and retinitis pigmentosa. Significantly increased protein level of IL-1β has been found in the vitreous of diabetic retinopathy patient. The role of IL-1β has been investigated for potential therapeutic target for treatment of diabetic retinopathy. However, systemic using of canakinumab did not have an significant effect. The role of IL-1β in age-related macular degeneration has not been proven in patient, but in many animal models and in vitro studies it has been demonstrated the role of IL-1β in retinal pigmented epithelial cells and photoreceptor cells damage. NLRP3 inflammasome activate caspase-1 which catalyze cleavage of inactive cytosolic precursor pro-IL-1β to its mature form IL-1β. Retinal pigmented epithelial cells forms blood retinal barrier in human retina which is important for retinal metabolic activity, integrity and inhibition of immune cells infiltration. It has been shown that human retinal pigmented epithelial cells can secrete IL-1 β in exposure to oxidative stress. The inflammatory reaction leads to damage of retinal cells and infiltration of cells of the immune system. The inflammatory process including NLRP3 upregulation is one of the causes of age-related macular degeneration and other retinal diseases that lead to vision loss.[26][27][28] Additionally, it has been shown that caspase-1 is upregulated in the retina of diabetic patients, causing a higher production of IL-1β and subsequent death of retinal neurons.[29]
Neuroinflammation
Studies in mice on experimental autoimmune encephalomyelitis (EAE), a model for multiple sclerosis (MS) research, have found that blocking IL-1β could make the animals resistant to EAE. IL-1β led to the production of an antigen-specific pro-inflammatory subset of T helper cells (TH17). In combination with other cytokines, interleukin-1β can upregulate the production of the cytokine GM-CSF which is correlated to neuroinflammation. Detailed mechanisms on this front are yet to be elucidated.[30]
IL-1β has also been observed in elevated levels of the cerebrospinal fluid and brain tissues of Alzheimer patients. The amyloid-β plaques, that are characteristic of Alzheimer disease, are damage-associated molecular patterns (DAMPs) that are recognized by pattern recognition receptors (PRRs) and lead to the activation of microglia. Consequently, microglia release interleukin-1β among other cytokines. Nevertheless, the significance of IL-1β in Alzheimer disease and the onset of neuroinflammation still remains largely unknown.[30]
Lastly, in vitro studies have shown that IL-1β causes an increase in mitochondrial glutaminase activity. In response, there is excessive glutamate secretion which has a neurotoxic effect.[30]
As a therapeutic target
Anakinra is a recombinant and slightly modified version of the human interleukin 1 receptor antagonist protein. Anakinra blocks the biologic activity of IL-1 alpha and beta by competitively inhibiting IL-1 binding to the interleukin type 1 receptor (IL-1RI), which is expressed in a wide variety of tissues and organs. Anakinra is marketed as Kineret and is approved in the US for treatment of RA, NOMID, DIRA.
Canakinumab is a human monoclonal antibody targeted at IL-1B, and approved in many countries for treatment of cryopyrin-associated periodic syndromes.
Orthographic note
Because many authors of scientific manuscripts make the minor error of using a homoglyph, sharp s (ß), instead of beta (β), mentions of "IL-1ß" [sic] often become "IL-1ss" [sic] upon automated transcoding (because ß transcodes to ss). This is why so many mentions of the latter appear in web search results.
References
- ^ a b c GRCh38: Ensembl release 89: ENSG00000125538 - Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000027398 - Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- PMID 6083565.
- ^ S2CID 4240002.
- PMID 3490654.
- PMID 2954882.
- PMID 22079.
- PMID 5033417.
- PMID 5033418.
- PMID 4549027.
- ^ S2CID 252762935.
- ^ "Entrez Gene: IL1B interleukin 1, beta".
- PMID 19682929.
- PMID 25625584.
- PMID 11683587.
- PMID 11759041.
- PMID 14642889.
- PMID 19302049.
- PMID 25274309.
- PMID 28583987.
- S2CID 160014053.
- PMID 30447690.
- PMID 29760166.
- PMID 29454857.
- PMID 23221073.
- PMID 31379825.
- PMID 28534174.
- ^ PMID 28534174.
- ^ "ARCALYSTTM (rilonacept) Product Label" (PDF). Regeneron Pharmaceuticals, Inc. U.S. Food and Drug Administration. Retrieved 5 October 2020.
Further reading
- Smirnova MG, Kiselev SL, Gnuchev NV, Birchall JP, Pearson JP (2003). "Role of the pro-inflammatory cytokines tumor necrosis factor-alpha, interleukin-1 beta, interleukin-6 and interleukin-8 in the pathogenesis of the otitis media with effusion". European Cytokine Network. 13 (2): 161–172. PMID 12101072.
- Griffin WS, Mrak RE (August 2002). "Interleukin-1 in the genesis and progression of and risk for development of neuronal degeneration in Alzheimer's disease". Journal of Leukocyte Biology. 72 (2): 233–238. PMID 12149413.
- Arend WP (2003). "The balance between IL-1 and IL-1Ra in disease". Cytokine & Growth Factor Reviews. 13 (4–5): 323–340. PMID 12220547.
- Chakravorty M, Ghosh A, Choudhury A, Santra A, Hembrum J, Roychoudhury S (February 2004). "Ethnic differences in allele distribution for the IL8 and IL1B genes in populations from eastern India". Human Biology. 76 (1): 153–159. S2CID 2816300.
- Joseph AM, Kumar M, Mitra D (January 2005). "Nef: "necessary and enforcing factor" in HIV infection". Current HIV Research. 3 (1): 87–94. PMID 15638726.
- Maruyama Y, Stenvinkel P, Lindholm B (2005). "Role of interleukin-1beta in the development of malnutrition in chronic renal failure patients". Blood Purification. 23 (4): 275–281. S2CID 72570361.
- Milosevic V, Kopecka J, Salaroglio IC, Libener R, Napoli F, Izzo S, et al. (January 2020). "Wnt/IL-1β/IL-8 autocrine circuitries control chemoresistance in mesothelioma initiating cells by inducing ABCB5". International Journal of Cancer. 146 (1): 192–207. S2CID 160014053.
- Roy D, Sarkar S, Felty Q (January 2006). "Levels of IL-1 beta control stimulatory/inhibitory growth of cancer cells". Frontiers in Bioscience. 11: 889–898. S2CID 23009646.
- Copeland KF (December 2005). "Modulation of HIV-1 transcription by cytokines and chemokines". Mini Reviews in Medicinal Chemistry. 5 (12): 1093–1101. PMID 16375755.
- Prinz C, Schwendy S, Voland P (September 2006). "H pylori and gastric cancer: shifting the global burden". World Journal of Gastroenterology. 12 (34): 5458–5464. PMID 17006981.
- Kamangar F, Cheng C, Abnet CC, Rabkin CS (October 2006). "Interleukin-1B polymorphisms and gastric cancer risk--a meta-analysis". Cancer Epidemiology, Biomarkers & Prevention. 15 (10): 1920–1928. S2CID 8542733.
External links
- IL1B+protein,+human at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
This article incorporates text from the United States National Library of Medicine, which is in the public domain.