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General Comment |
This gene encodes a SASP.
As reviewed in Dinarello (1994), two structurally distinct forms of IL1 exist: IL-1-a, the acidic form, and IL-1b, the neutral form. Both are 17-kD proteins coded by separate genes. The IL-1 system is also made up of one receptor antagonists (IL-1RA) and at least two receptors (IL-1 Receptor type I and Type II, or IL-1R tI and Il-1R tII). A receptor accessory protein (IL-1RAcP) has also been shown to interact IL-1R tII (Lang et al., 1998). /////////senescence
NCBI Summary:
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. [provided by RefSeq, Jul 2008]
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Comment |
Hurwitz et al. (1992) studied the role of IL1 in the ovary, using a solution hybridization/RNase protection assay to test for expression of the IL1 gene, its type I receptor (IL1R; 147810), and its receptor antagonist (IL1RA). Their findings revealed the existence of a complete, highly compartmentalized, hormone-dependent intraovarian IL1 system. IL-1 plays important roles in follicle development, steroidogenesis, ovulation, and luteal function (Terranova et al, 1997). Hogquist et al. (1991) demonstrated that both interleukin-1 a and b are involved in apoptosis (cell death). Also, the presence of
IL-1alpha and IL-1beta in oocyte-conditioned media and on the surface of human oocytes suggests that interleukins may also be involved in oocyte growth and/or maturation (de los Santos et al., 1998).
Gene whose expression is detected by cDNA array hybridization: stress response, cell/cell communication Rozenn Dalbi?Tran and Pascal Mermilloda
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Comment |
A morphological study by Simon et al. (1994) suggested an autocrine-paracrine role of the IL-1 system (including IL-1a, IL-1b, IL-1R tI) in the murine ovary. Ligands and receptor were identified in theca-interstitial layers during follicular development. Strong IL-1 staining was also found in the cytoplasm and plasma membrane of the oocyte. Just before follicular rupture, IL-R t1 staining was observed in cumulus and granulosa cells. During ovulation, IL-1a and IL-1b staining was found in the theca layer. After ovulation, IL-1a and IL-1b, and IL-1R tI were found in the granulosa-luteal cells of the developing corpus luteum.
In humans, the IL-1 system as been localized to granulosa cells, luteal cells, ovarian surface epithelium, whole ovary, and follicular fluid (Terranova et al., 1997). Also, de los Santos et al.(1998) found IL-1alpha and IL-1beta in oocyte-conditioned media and on the surface of human oocytes.
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Mutations |
4 mutations
Species: mouse
Mutation name: None
type: null mutation
fertility: subfertile
Comment: Interleukin-1 deficiency prolongs ovarian lifespan in mice. Uri-Belapolsky S 2014 et al.
Oocyte endowment dwindles away during prepubertal and adult life until menopause occurs, and apoptosis has been identified as a central mechanism responsible for oocyte elimination. A few recent reports suggest that uncontrolled inflammation may adversely affect ovarian reserve. We tested the possible role of the proinflammatory cytokine IL-1 in the age-related exhaustion of ovarian reserve using IL-1a and IL-1-KO mice. IL-1a-KO mice showed a substantially higher pregnancy rate and litter size compared with WT mice at advanced age. The number of secondary and antral follicles was significantly higher in 2.5-mo-old IL-1a-KO ovaries compared with WT ovaries. Serum anti-Mllerian hormone, a putative marker of ovarian reserve, was markedly higher in IL-1a-KO mice from 2.5 mo onward, along with a greater ovarian response to gonadotropins. IL-1-KO mice displayed a comparable but more subtle prolongation of ovarian lifespan compared with IL-1a-KO mice. The protein and mRNA of both IL-1a and IL-1 mice were localized within the developing follicles (oocytes and granulosa cells), and their ovarian mRNA levels increased with age. Molecular analysis revealed decreased apoptotic signaling [higher B-cell lymphoma 2 (BCL-2) and lower BCL-2-associated X protein levels], along with a marked attenuation in the expression of genes coding for the proinflammatory cytokines IL-1, IL-6, and TNF-a in ovaries of IL-1a-KO mice compared with WT mice. Taken together, IL-1 emerges as an important participant in the age-related exhaustion of ovarian reserve in mice, possibly by enhancing the expression of inflammatory genes and promoting apoptotic pathways.
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Species: human
Mutation name:
type: naturally occurring
fertility: subfertile
Comment: Interleukin-1 alpha but not interleukin-1 beta gene polymorphism is associated with polycystic ovary syndrome. Kolbus A et al. (2007) Interleukin-1 (IL1) is a multifunctional cytokine and IL1-mediated inflammatory processes have been proposed to influence the processes of ovulation, fertilization and implantation. All these parameters are also affected in women with polycystic ovary syndrome (PCOS). This study investigated the association of common polymorphisms of the interleukin-1 genes (IL1A and IL1B) with the occurrence and clinical characteristics of PCOS. We evaluated one polymorphism of the IL1alpha gene (IL1A C[-889]T) and two of the IL1beta gene (IL1B promoter C[-511]T and IL1B exon 5 position +3953) in 105 Caucasian women with PCOS and 102 healthy Caucasian controls by polymerase chain reaction. For the mutated IL1A allele, allele frequencies in women with PCOS and controls were 60% and 46%, respectively, versus 40% and 54%, respectively, for the wild type allele. Allele frequencies in women with PCOS and controls were 59% (54%) and 61% (41%), respectively, for the mutated IL1B promoter (mutated IL1B exon 5) and 41% (46%) and 39% (59%), respectively, for the wild type alleles. Presence of a polymorphism in the interleukin-1alpha but not the interleukin-1beta gene was found to correlate with the occurrence of PCOS (p=0.04; odds ratio 1.8). The serum level of FSH and subsequent LH/FSH ratio correlated with the polymorphism of IL1A within the PCOS group (p=0.005 and 0.01, respectively). We have shown that a common polymorphism of the interleukin-1alpha but not interleukin-1beta gene is associated with the presence of PCOS and with clinical parameters of women affected by this condition.//////////////////
Species: human
Mutation name:
type: naturally occurring
fertility: None
Comment: The effects of IL-1A and IL-6 genes polymorphisms on gene expressions, hormonal and biochemical parameters in polycystic ovary syndrome. Eser B et al. (2016) Polycystic ovary syndrome (PCOS) is a multifactorial disease characterised by chronic inflammation. We aimed to investigate an association between IL-1A and IL-6 gene polymorphisms and both hormonal/biochemical parameters and levels of IL-1A and IL-6. A total of 103 women diagnosed with PCOS according to ESHRE/ASRM criteria were investigated. The patients were divided into two groups as obese and non-obese. IL-1A and IL-6 genes polymorphisms as well as hormonal/biochemical parameters and levels of IL-1A and IL-6 were analysed in the same groups. Serum IL-1A and IL-6 levels were found to increase both in obese and non-obese groups. However, there was no association between IL-1A level and IL-1A polymorphism. A relationship was detected between H score, FSH, LH, total testosterone, HDL-C and TG levels and CG + GG genotypes of IL-6. Furthermore, an association was found between IL-6 levels and CC genotype of IL-6 in the obese PCOS patients. The abnormalities in hormonal/biochemical parameters detected in Turkish PCOS patients may be related with IL-6 gene polymorphism rather than IL-1A.//////////////////
Species: mouse
Mutation name:
type: null mutation
fertility: None
Comment: Interleukin 1-alpha deficiency increases the expression of follicle stimulating hormone receptors in granulosa cells. Uri-Belapolsky S et al. (2017) Follicle-stimulating hormone receptor (FSHR) is a pivotal regulator of ovarian response to hormonal stimulation. Inflammatory conditions have been linked to lower FSHR expression in granulosa cells (GCs) as well as an attenuated response to hormonal stimulation. The current study aimed to reveal if deficiency and/or blockage of the pro-inflammatory cytokine interleukin 1-alpha (IL1A) increased Fshr expression in rodent GCs. We found elevated Fshr transcript abundance, as assessed by quantitative PCR, in primary GCs isolated from Il1a-knockout compared to wild-type mice, and that the expression of FSHR is significantly higher in Il1a-knockout compared to wild-type ovaries. Supplementing GC cultures with recombinant IL1A significantly lowered Fshr expression in these cells. In accordance with the Fshr expression pattern, proliferation of GCs was higher in follicles from Il1a-knockout mice compared to wild-type mice, as indicated by the MKI67 immunohistochemical staining. Furthermore, treating wild-type mice with anakinra, an IL1 receptor 1 antagonist, significantly increased the expression of Fshr in primary GCs from treated compared to control mice. These data highlight an important interdependency between the potent pro-inflammatory cytokine IL1A and Fshr expression. This article is protected by copyright. All rights reserved.//////////////////
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