HCSGD entry for IL1A


1. General information

Official gene symbolIL1A
Entrez ID3552
Gene full nameinterleukin 1, alpha
Other gene symbolsIL-1A IL1 IL1-ALPHA IL1F1
Links to Entrez GeneLinks to Entrez Gene

2. Neighbors in the network

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3. Gene ontology annotation

GO ID

GO term

Evidence

Category

GO:0001660Fever generationIEAbiological_process
GO:0005125Cytokine activityIMPmolecular_function
GO:0005149Interleukin-1 receptor bindingIEAmolecular_function
GO:0005507Copper ion bindingIDAmolecular_function
GO:0005515Protein bindingIPImolecular_function
GO:0005576Extracellular regionTAScellular_component
GO:0005615Extracellular spaceIDA IMPcellular_component
GO:0005829CytosolIDAcellular_component
GO:0006915Apoptotic processTASbiological_process
GO:0006954Inflammatory responseTASbiological_process
GO:0006955Immune responseIEAbiological_process
GO:0008283Cell proliferationTASbiological_process
GO:0008285Negative regulation of cell proliferationIDAbiological_process
GO:0010575Positive regulation vascular endothelial growth factor productionISSbiological_process
GO:0019221Cytokine-mediated signaling pathwayIMPbiological_process
GO:0034605Cellular response to heatIDAbiological_process
GO:0035234Ectopic germ cell programmed cell deathIEAbiological_process
GO:0045086Positive regulation of interleukin-2 biosynthetic processIMPbiological_process
GO:0045766Positive regulation of angiogenesisISSbiological_process
GO:0045840Positive regulation of mitosisIMPbiological_process
GO:0045944Positive regulation of transcription from RNA polymerase II promoterIEAbiological_process
GO:0046688Response to copper ionIDAbiological_process
GO:0050715Positive regulation of cytokine secretionIDAbiological_process
GO:0051781Positive regulation of cell divisionIEAbiological_process
GO:0097192Extrinsic apoptotic signaling pathway in absence of ligandIEAbiological_process
GO:2001240Negative regulation of extrinsic apoptotic signaling pathway in absence of ligandTASbiological_process
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4. Expression levels in datasets

  • Meta-analysis result

p-value upp-value downFDR upFDR down
0.00002652250.97806456060.01490638301.0000000000

  • Individual experiment result
    ( "-" represent NA in the specific microarray platform )

Data sourceUp or downLog fold change
GSE11954Up1.0377099751
GSE13712_SHEARUp1.5116505723
GSE13712_STATICUp1.0891805328
GSE19018Down-0.1546128326
GSE19899_A1Up3.3379862512
GSE19899_A2Up4.2324232933
PubMed_21979375_A1Up3.2008029256
PubMed_21979375_A2Up4.8739964362
GSE35957Up0.7169967783
GSE36640Down-0.6040899813
GSE54402Up1.9603504051
GSE9593Down-0.0805325239
GSE43922Up6.4216320709
GSE24585Up0.6435307736
GSE37065Up1.6857110436
GSE28863_A1Down-0.1030764931
GSE28863_A2Down-0.0030541664
GSE28863_A3Up0.0058732636
GSE28863_A4Down-0.1063579025
GSE48662Up0.0779317776

5. Regulation relationships with compounds/drugs/microRNAs

  • Compounds

Not regulated by compounds

  • Drugs

Name

Drug

Accession number

RilonaceptDB06372 -

  • MicroRNAs

    • mirTarBase

MiRNA_name

mirBase ID

miRTarBase ID

Experiment

Support type

References (Pubmed ID)

hsa-miR-191-5pMIMAT0000440MIRT004689Immunohistochemistry//Immunoprecipitaion//Luciferase reporter assay//Microarray//qRT-PCRFunctional MTI20924108
hsa-miR-335-5pMIMAT0000765MIRT017051MicroarrayFunctional MTI (Weak)18185580
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    • mirRecord
No target information from mirRecord

6. Text-mining results about the gene

Gene occurances in abstracts of cellular senescence-associated articles: 21 abstracts the gene occurs.


PubMed ID of the article

Sentenece the gene occurs

27306980Cells undergoing senescence acquire a senescence associated secretory phenotype (SASP) leading to the production of interleukin-1 alpha (IL-1alpha), which has been implicated in several degenerative and inflammatory processes including renal disease
26199639Moreover, bavachalcone suppressed senescence in human endothelial cells and mRNA expression of p16(ink4a) (a marker of replicative senescence) and IL-1alpha (a proinflammatory cytokine of the senescence-associated secretory phenotype)
26147250MTOR regulates the pro-tumorigenic senescence-associated secretory phenotype by promoting IL1A translation
26147250Rapamycin reduced IL6 and other cytokine mRNA levels, but selectively suppressed translation of the membrane-bound cytokine IL1A
26147250Reduced IL1A diminished NF-kappaB transcriptional activity, which controls much of the SASP; exogenous IL1A restored IL6 secretion to rapamycin-treated cells
26069700The effect of osteogenic protein-1 (OP-1) or interleukin-1alpha (IL-1alpha) treatment on telomerase activity in chondrocytes was also measured to determine the response to anabolic or catabolic stimuli
26069700Chondrocytes from prepubescent horses (<15 months) were treated with OP-1 or IL-1alpha
26069700Treatment with IL-1alpha resulted in a decrease in chondrocyte telomerase activity; however, treatment with OP-1 did not change telomerase activity
24827852Furthermore, quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR) analysis revealed activation of the senescence-associated secretory phenotype (SASP), including the cytokines interleukin 6 (IL6) and 1alpha (IL1alpha)
24434012Multiplex analysis revealed that multiple cytokines are increased in BPH, including GM-CSF, IL-1alpha, and IL-4, and that these are also increased in senescent prostatic epithelial cells in vitro
24434012IHC analysis revealed the multifocal epithelial expression of cathepsin D and coexpression with IL-1alpha in BPH tissues
24434012In tissue recombination studies in nude mice with immortalized prostatic epithelial cells expressing IL-1alpha and prostatic stromal cells, both epithelial and stromal cells exhibited increased growth
24434012Expression of IL-1alpha in prostatic epithelial cells in a transgenic mouse model resulted in increased prostate size and bladder obstruction
24062309Redox control of the senescence regulator interleukin-1alpha and the secretory phenotype
24062309IL-1alpha is a key senescence-associated (SA) proinflammatory cytokine that acts as a critical upstream regulator of the SA secretory phenotype (SASP)
24062309We established that SA shifts in steady-state H2O2 and intracellular Ca(2+) levels caused an increase in IL-1alpha expression and processing
24062309The increase in intracellular Ca(2+) promoted calpain activation and increased the proteolytic cleavage of IL-1alpha
24062309Ca(2+) chelation or calpain inhibition prevented SA processing of IL-1alpha and its ability to induce downstream cytokine expression
24062309Collectively, these findings demonstrate how SA alterations in the redox state and Ca(2+) homeostasis modulate the inflammatory phenotype through the regulation of the SASP initiator IL-1alpha, creating a microenvironment permissive to tumor invasion
23770676The inflammasome and IL-1 signalling are activated in senescent cells and IL-1alpha expression can reproduce SASP activation, resulting in senescence
22404905Suppression of the prototypical SASP component IL-6 required the glucocorticoid receptor, which, in the presence of ligand, inhibited IL-1alpha signaling and NF-kappaB transactivation activity
22404905Accordingly, co-treatments combining glucocorticoids with the glucocorticoid antagonist RU-486 or recombinant IL-1alpha efficiently reestablished NF-kappaB transcriptional activity and IL-6 secretion
22319624Both fatty acids appeared to abolish H(2)O(2) mediated stimulation of nuclear factor kappaB and IL-6, but not IL-1alpha and IL-8
19805069Cell surface-bound IL-1alpha is an upstream regulator of the senescence-associated IL-6/IL-8 cytokine network
19805069We show that cell surface-bound IL-1alpha is essential for signaling the senescence-associated secretion of IL-6 and IL-8, 2 proinflammatory cytokines that also reinforce the senescence growth arrest
19805069An IL-1 receptor (IL1R) antagonist, neutralizing IL-1alpha antibodies, and IL-1alpha depletion by RNA interference all markedly reduced senescence-associated IL-6/IL-8 secretion
19805069Furthermore, IL-1alpha depletion reduced the DNA binding activity of NF-kappaB and C/EBPbeta, which stimulate IL-6/IL-8 transcription
19805069IL-1alpha was a general regulator of senescence-associated IL-6/IL-8 secretion because IL-1alpha blockade reduced IL-6/IL-8 secretion whether cells senesced owing to DNA damage, replicative exhaustion, oncogenic RAS, or chromatin relaxation
19805069Furthermore, conditioned medium from IL-1alpha-depleted senescent cells markedly reduced the IL-6/IL-8-dependent invasiveness of metastatic cancer cells, indicating that IL-1alpha regulates the biological effects of these cytokines
19805069Thus, cell surface IL-1alpha is an essential cell-autonomous regulator of the senescence-associated IL-6/IL-8 cytokine network
19027816Resveratrol treatment effectively prevented increased production of intracellular reactive oxygen species (iROS) and inflammatory markers (IL1alpha, IL6, IL8, and ELAM-1), and reduced expression of the senescence markers sa-beta-gal, lipofuscin, and accumulation of carbonylated proteins
16280018On the other hand, a significant positive correlation existed between age and interleukin ((IL)-1alpha secretion (R2=0
16280018The IL-1alpha secretion by keratinocytes was significantly increased in the fifth cultures compared with the second cultures (P<0
16280018CONCLUSIONS: These findings suggest that IL-1alpha secretion increases as cells grow older, and the increased secretion of IL-1alpha by aged keratinocytes may stimulate HGF production in dermal fibroblasts paracrinely and ET-1 production in keratinocytes autocrinely, which stimulates melanocyte proliferation and induces an increase of tyrosinase activity in melanocytes
16280018Because IL-1alpha is a primary mediator that responds to inflammation and injury, the transcription of genes involved in skin inflammation may be persistently induced in the aged skin
16280018Thus the increased secretion of IL-1alpha by aged keratinocytes in the aged skin may play a role in the accentuated cutaneous pigmentation and other skin ageing
12640658In BPH, there is an increased expression of Il-1alpha by prostatic epithelial cells that results in elevated expression of FGF7 by stromal cells, which in turn is strongly correlated with epithelial proliferation
12640658Il-1alpha expression was localized by immunohistochemistry and Il-1alpha tissue content determined by enzyme-linked immunoabsorption assay
12640658RESULTS: Expression of Il-1alpha is significantly increased in vitro when cultured prostatic epithelial cells undergo senescence
12640658By quantitative assay, SA-beta gal activity is correlated with both tissue levels of Il-1alpha and the severity of BPH
12640658CONCLUSIONS: One mechanism driving BPH in older men is the accumulation of senescent epithelial cells expressing Il-1alpha, which in turn increases FGF7 secretion and proliferation of non-senescent epithelial cells
8972724The human diploid fibroblast senescence pathway is independent of interleukin-1 alpha mRNA levels and tyrosine phosphorylation of FGFR-1 substrates
8972724In vitro cellular senescence of human umbilical vein endothelial cells (HUVEC) may involve the intracellular activity of the signal peptide-less cytokine interleukin (IL)-1 alpha
8972724To determine whether senescence of other human diploid cells involves the function of IL-1 alpha, we examined the steady-state expression of IL-1 alpha mRNA in IMR-90 fibroblasts
8972724The IL-1 alpha transcript was not elevated in senescent IMR-90 cells
8972724With the exception of the plasminogen activator inhibitor (PAI)-1 transcript, other IL-1 alpha-response gene mRNAs were not induced in senescent IMR-90, although the mRNA for each gene was induced by exogenous IL-1 alpha
8972724These data demonstrate that IL-1 alpha and FGF-1 may have different functions in HUVEC and IMR-90 fibroblast populations including distinct pathways for the regulation of cellular growth and senescence
7628547Interestingly the increase of PAI-1 levels correlates with the upregulation of interleukin 1 alpha, which characterizes endothelial cell senescence
7628547Moreover, PAI-1 was not upregulated in senescent or in progeric human fibroblasts, which do not overexpress interleukin 1 alpha, thus suggesting that multiple pathways may exist to regulate aging of human fibroblasts and endothelial cells
8114717Endogenous interleukin 1 alpha must be transported to the nucleus to exert its activity in human endothelial cells
8114717We have previously shown that the signal peptideless cytokine interleukin 1 alpha (IL-1 alpha) may play a role as an intracellular regulator of human endothelial cell senescence (J
8114717To investigate the potential intracellular function of IL-1 alpha, transformed endothelial cells were transfected with the human cDNAs that code for the two forms of IL-1 alpha, the precursor molecule IL-1(1-271) and the mature protein IL-1(113-271)
8114717The subcellular localization of the two different polypeptides was investigated directly or by using chimeric genes constructed by fusion of different fragments of the IL-1 alpha gene and the beta-galactosidase open reading frames
8114717The basic cluster at the NH2 terminus of IL-1, KVLKKRR, has been shown to mediate IL-1 alpha nuclear targeting
8114717Moreover, nuclear localization of IL-1 alpha correlates with impaired cell growth and expression of some IL-1 alpha-inducible genes
8359220Here we show that (i) senescence enhances monoblastoid U937 cell adhesion to the endothelial monolayer; (ii) the enhanced interaction between senescent endothelial cells and U937 cells is mediated, at least in part, by the overexpression of ICAM-1; and (iii) LPS and interleukin 1 alpha, but not tumor necrosis factor alpha, are unable to stimulate the adhesion of U937 to senescent endothelial cells
1322316Interleukin-1 alpha treatment increased collagenase and stromelysin mRNA levels while transforming growth factor-beta reduced the steady-state levels of both transcripts
1716619Epidermal growth factor and its receptor, basic fibroblast growth factor, transforming growth factor beta-1, and interleukin-1 alpha messenger RNA production in human corneal endothelial cells
1716619The authors tried to determine whether human corneal endothelial cells in primary culture synthesize messenger RNA (mRNA) coding for epidermal growth factor (EGF), EGF receptor, basic fibroblast growth factor (FGFb), transforming growth factor beta-1 (TGFb1), and interleukin-1 alpha (IL-1 alpha)
1716619The polymerase chain reaction (PCR) was used to amplify the growth factors (EGF, FGFb, TGFb1, and IL-1 alpha), EGF receptor, and beta actin sequences from each of the cDNA samples
1716619The EGF mRNAs were detected by PCR alone in four of the samples from proliferative cultures, TGFb1 mRNAs in three, and IL-1 alpha mRNAs in three
2218499Extension of the life-span of human endothelial cells by an interleukin-1 alpha antisense oligomer
2218499Senescent human endothelial cells were shown to contain high amounts of the transcript for the cytokine interleukin-1 alpha (IL-1 alpha), a potent inhibitor of endothelial cell proliferation in vitro
2218499In contrast, transformed human endothelial cells did not contain detectable IL-1 alpha messenger RNA
2218499Treatment of human endothelial cell populations with an antisense oligodeoxynucleotide to the human IL-1 alpha transcript prevented cell senescence and extended the proliferative life-span of the cells in vitro
2218499Removal of the IL-1 alpha antisense oligomer resulted in the generation of the senescent phenotype and loss of proliferative potential
2218499These data suggest that human endothelial cell senescence in vitro is a dynamic process regulated by the potential intracellular activity of IL-1 alpha
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