Protein IL1A

URN urn:agi-llid:3552
Name IL1A
Description interleukin 1 alpha
Connectivity 816
Notes (125)I fibrinogen demonstrated no specific interaction of IL-1alpha with fibrinogen (125)I fibrinogen demonstrated no specific interaction of IL-1alpha with fibrinogen. A potent cytokine stimulus for IL-8 RNA stabilization in breast cancer cells. Activation of vascular endothelial cells by IL-1alpha released by a pulmonary epithelial cell line infected with respiratory syncytial virus. Allele specific regulation of cytokine genes: monoallelic expression of the IL-1A gene. Review. Association of the interleukin-1 gene cluster on chromosome 2q13 with knee osteoarthritis. Cancer cell-derived cytokines, such as IL-1 alpha, induce cachexia by affecting leptin-dependent metabolic pathways. Cellular and subcellular expression of TNF-alpha, IL-1alpha and IL-6 in hepatocytes inx chronic hepatitis C. Cloning and functional analysis of the allelic polymorphism in the transcription regulatory region. Data demonstrates that IL-1alpha and COX-2 mRNA are frequently co-expressed in human gastric cancer tissues, and suggest that the IL-1alpha-COX-2 pathway might be involved in tumor progression by regulating cancer cell proliferation. Data show that interleukin 1-alpha (IL-1a) is an important autocrine fibrogenic factor in systemic sclerosis (SSc) and suggest that inhibition of intracellular IL-1a may be a novel strategy for the treatment of SSc. IL-1 evokes a complex gene expression program in endothelial cells that includes positive but also negative (feedback) regulators of diverse endothelial cell functions. IL-1-inducible phosphorylation of p65 NFkB is mediated by multiple protein kinases including IKKalpha, IKKbeta, IKKepsilon, TBK1, and an unknown kinase and couples p65 to TAFII31-mediated IL-8 transcription. IL-1A allele 2 is a risk factor for Alzheimer's disease (AD) in a dose-dependent manner, the risk of developing AD with two copies of the IL-1A allele 2 being approximately double that of one copy of the IL-1A allele 2. IL-1A was used to stimulate epidermal keratinocytes in organ culture. IL-1alpha activity in chondrocytes is independent of any direct modification in UDPGD activity and manifests equally in human cartilage of all ages. IL-1alpha, TNF-alpha, CCL20, CCL27, and CXCL8 alarm signals are induced in human cells after allergen and irritant exposure. IL-1beta is the critical regulator of tuberculosis-stimulated CCL5 secretion in the lung. IL1-alpha induced during in vitro activation of mast cells by cystic fibrosis-associated Pseudomonas aeruginosa stimulates neutrophil transendothelial migration. In IL-1 alpha transgenic mice, which may overproduce membrane-associated (MA)IL-1 as well as soluble IL-1 alpha, severity of arthritis highly correlates with MA-IL-1 activity rather than with soluble IL-1 alpha activity or serum IL-1 alpha concentration. In conjunctiva of keratoconjunctivitis sicca patients. In pancreatic cancer, IL-1alpha enhanced alpha(6)beta(1)-integrin expression, probably via increased IL-1RI levels. Interleukin-1 alpha and beta system in testis--quantitative analysis. Expression of immunomodulatory genes in male gonad. Interleukin-1 system plays a role in sex steroid receptor gene expression in human endometrial cancer. Lipopolysaccharide-mediated reactive oxygen species and signal transduction in the regulation of interleukin-1 gene expression. Low levels of IL-1 alpha mrna expression are associated with an increased risk for cancer specific death in patients with bladder cancer. Monoallelic expression of IL-1 alpha is observed in Th0, Th1, and Th2 cell clones from healthy individuals, as well as in synovial fluid of the knee joint derived from rheumatoid arthritis patients. Potential in tissue repair for injured human keratinocytes. Precursor form of IL-1alpha was overexpressed in various cells and assessed for activity in the presence of saturating concentrations of IL-1 receptor antagonist. Proapoptotic stimuli upregulate MCP-1 expression by vascular smooth muscle cells through release of interleukin-1alpha. Results suggest a role for the IL1A gene in modifying the clinical features of migraine. Review. The IL-1 family consists of IL-1alpha and IL-1beta, 2 receptors, and a specific receptor antagonist, IL-1Ra. The balance between IL-1 & IL-1Ra in local tissues plays an important role in the susceptibility to & severity of many diseases. Review.inheritance of a specific IL-1A gene polymorphism increases risk for development of Alzheimer's disease by as much as sixfold. Moreover, this increased risk is associated with earlier age of onset of the disease. SHP-2 has a role in regulating IL-1-induced Ca2+ flux and ERK activation via phosphorylation of PLCgamma1. TNF-alpha & IL-1 produced by sickle leukocytes are the primary factors responsible for the observed CAM expression. This & the subsequent endothelial adherence of sickle erythrocytes play roles in the pathophysiology of sickle-related complications. TNF-alpha promoter polymorphism is associated with Il-1 beta synthesis capacity in human leukocytees. The IL-1alpha-889 polymorphism, previously shown to predispose to increased IL-1 protein expression, may be involved in susceptibility to systemic sclerosis. The IL1A genotype associates with atopy in nonasthmatic adults. The association of the TN7(delTTCA)A haplotype with higher levels of IL-1 alpha expression and reduced risk for ESRD is consistent with involvement of cytokines in risk for developing nephropathy. The level of IL-1 alpha is significantly higher in sera of cicatricial pemphigoid patients with active disease before intravenous immunoglobulin therapy compared to the post-treatment level. The presence of high amounts of intracellular IL-1alpha in human dermal fibroblasts suggests that these cytokines may carry out important function inside cells. The protein encoded by this gene is a member of the interleukin 1 cytokine family. This cytokine is a pleiotropic cytokine involved in various immune responses, inflammatory processes, and hematopoiesis. This cytokine is produced by monocytes and macrophages as a proprotein, which is proteolytically processed and released in response to cell injury, and thus induces apoptosis. This gene and eight other interleukin 1 family genes form a cytokine gene cluster on chromosome 2. It has been suggested that the polymorphism of these genes is associated with rheumatoid arthritis and Alzheimer's disease. The proteolytic activation of pro-MMP-9 in skin inflammatory diseases likely occurs via a pathway including IL-1alpha. The results suggest a possible contribution of the IL-1 gene locus polymorphisms to the pathogenesis of LBP. The significant associations between VEGF and the levels of IL6 and IL1 alpha suggest an important role for these cytokines in the development of these tumours. Two polymorphisms within the IL-1 gene cluster are associated with ESRD independent of race. We have identified a novel regulatory sequence at -65 to -41 of the human IL-1alpha promoter. White carriers of the (+484)T haplotype were at increase risk of spontaneous preterm birth. A ""defective"" IL-1ra response to IL-1 may underlie, at least in part, the exaggerated prostaglandin-endoperoxide H synthase (PGHS)-2 induction in orbital fibroblasts. Cells of keratinocyte origin (SCC 12F) respond to a single physiologic dose of solar-simulated irradiation with both early (8 h) and late (72 h) peaks of IL-1alpha mRNA induction. Confirm the role of uPA in acantholysis and suggest an involvement of IL-1alpha/TNF-alpha in uPA induction. Data indicate that IL-1 gene polymorphisms known to affect the inflammatory response are highly related to plasma levels of CRP and fibrinogen in patients referred for coronary angiography. Essential role for soluble factors, mainly IL-1alpha and bFGF, in the stimulation of dermal fibroblasts by human melanoma cells to secrete MMP-1. Individuals carrying the positive genotype have significantly greater risk for developing periodontitis. Investigated interleukin polymorphisms in ovarian cancer but did not find any association between common polymorphisms of interleukin 1A, interleukin 1B, and interleukin 1 receptor antagonist and the occurrence of ovarian cancer. May enhance the local production of CCL3, which may interact with CCR1 expressed on hepatoma cells, in an autocrine and/or paracrine manner. No one particular polymorphism in the IL-1 gene cluster yields an advantage for survival in the last decades of life. Polymorphisms may play an important role in determining generalized aggressive periodontits susceptibility in Chinese males. Polymorphisms of IL1A (G/T at +4845) and IL4RA (T/C at +22446) show an epistatic effect on the risk of atopy. Relationship between interleukin-1A (IL-1A) gene polymorphisms and the susceptibility of chronic periodontitis in Uighur minority in Xingjiang province of China. Serum IL-1 alpha and IL-1 soluble receptor type 2 levels in women with ovarian cancers were significantly higher than those in cervical cancer, and in patients with benign disorders, and in healthy control. Serum IL-1 and TNF-alpha are reduced significantly by calcitriol during osteoporosis. Soluble form of the IL-1 receptor accessory protein (AcP) increases the affinity of binding of human IL-1alpha and IL-1beta to the soluble human type II IL-1 receptor. That a DNA binding protein containing the Ets domain is constitutively expressed in fibroblasts from the skin of systemic sclerosis patients and regulates transcription of the IL1A gene, contributing to the fibrogenic phenotype of fibroblasts. The CTG haplotype of the IL1A gene may be an important marker for the susceptibility to, and the severity of, systemic sclerosis. The constitutively up-regulated expression of pre-IL-1 alpha in the nuclei of systemic sclerosis (SSc) fibroblasts up-regulates proliferation and matrix production of SSc fibroblasts through binding necdin.

KEGG pathway Hematopoietic cell lineage
Type I diabetes mellitus
Apoptosis
Cytokine-cytokine receptor interaction
MAPK signaling pathway

Swiss-Prot Accession P01583
Q53QF9
P01582
Q3U0Y6
Q62161
P16598
Q71VD0
Q9ESW2
Q546R9

Unigene ID Hs.1722
Mm.15534
Rn.12300

KEGG ID hsa:3552
mmu:16175
rno:24493

Swiss-Prot ID IL1A_HUMAN
IL1A_MOUSE
IL1A_RAT
Q53QF9_HUMAN
Q3U0Y6_MOUSE

Cell Localization Extracellular

GO ID 0005125
0005149
0005515
0006916
0006915
0019221
0001660
0006955
0006954
0008285
0045766
0050715
0045086
0045840
0010575
0005576
0005615
0008083
0008283
0005150
0004871
0007267
0006935
0005737
0000074

Pathway IL1R -> STAT3 signaling
IL1R -> NF-kB signaling
VDR Targets

IPI ID IPI00003096
IPI00136895
IPI00213945
IPI00192438
IPI00781873

Ariadne Ontology IL1 family

Mouse chromosome position 2 73.0 cM

GO Molecular Function protein binding
growth factor activity
cytokine activity
interleukin-1 receptor binding
interleukin-1, Type I receptor binding

Homologene ID 480

Hugo ID 5991

GO Cellular Component extracellular region
extracellular space

MGI ID 96542

Human chromosome position 2q14

GO Biological Process positive regulation of angiogenesis
negative regulation of cell proliferation
anti-apoptosis
positive regulation of mitosis
positive regulation of interleukin-2 biosynthetic process
positive regulation vascular endothelial growth factor production
positive regulation of cytokine secretion
cytokine-mediated signaling pathway
fever
cell proliferation
apoptosis
immune response
inflammatory response

Rat chromosome position 3q36

GenBank ID NC_000002
NM_000575
NP_000566
NT_022135
NW_001838841
NW_921474
AC_000134
AC_000045
AC079753
AC112235
AAX93054
AF536338
AAM96189
BN000002
CAD29871
CH471217
EAW73604
X03833
CAA27448
AK314850
BAG37367
BC013142
AAH13142
BC035169
BT007014
AAP35660
CA307202
CR457414
CAG33695
M15329
AAA59133
X02531
CAA26371
X02851
CAA26604
X56086
CAA39566
P01583
Q53QF9
DQ890675
ABM81601
DQ893856
ABM84782
NC_000068
NM_010554
NP_034684
NT_039207
NW_001030694
AC_000024
AF010237
AAC28999
AL772347
CAM15804
AY902318
AAX90603
CH466519
EDL28236
EDL28237
AK156449
BAE33715
BC003727
AAH03727
M14639
AAA40058
X01450
CAA25682
P01582
Q3U0Y6
Q62161
NC_005102
NM_017019
NP_058715
NW_047658
NW_001084813
AC_000071
AF016188
AAD01583
CH473949
EDL80161
EDL80162
AJ245642
CAC03995
AJ245643
CAC03996
D00403
BAA00306
P16598
Q71VD0
Q9ESW2
Q546R9
NW_000178

Group IL1 family
extracellular region
extracellular space
protein binding
growth factor activity
cytokine activity
interleukin-1 receptor binding
interleukin-1, Type I receptor binding
positive regulation of angiogenesis
negative regulation of cell proliferation
anti-apoptosis
positive regulation of mitosis
positive regulation of interleukin-2 biosynthetic process
positive regulation vascular endothelial growth factor production
positive regulation of cytokine secretion
cytokine-mediated signaling pathway
fever
cell proliferation
apoptosis
immune response
inflammatory response

RGD ID 2890

LocusLink ID 3552
16175
24493

Alias IL1
IL-1A
IL1F1
IL1-ALPHA
interleukin 1, alpha
IL1A (IL1F1)
hematopoietin-1
preinterleukin 1 alpha
pro-interleukin-1-alpha
RP23-160G19.8
interleukin 1 alpha
OTTMUSP00000016430
IL-1 alpha
interleukin-1 alpha
IL1 alpha
IL1A
Interleukin-1 alpha subunit
Interleukin-1 large subunit
preinterleukin 1
preinterleukin I
Hematopoietin I
IL1F I

Organism Homo sapiens
Mus musculus
Rattus norvegicus

OMIM ID 147760