Interleukin-1 consists of 2 separate but related proteins (IL1-alpha and IL1-beta). Dower et al. (1986) showed that the cell surface receptors for the two forms of interleukin-1 are identical. Sims et al. (1989) cloned the human IL1R gene and compared it with the mouse gene. Both contain a single membrane-spanning segment, a large cytoplasmic region, and an extracellular, IL1-binding portion composed of 3 immunoglobulin-like domains.
NCBI Summary:
The protein encoded by this gene is a cytokine receptor that belongs to the interleukin 1 receptor family. This protein is a receptor for interleukin alpha (IL1A), interleukin beta (IL1B), and interleukin 1 receptor, type I(IL1R1/IL1RA). It is an important mediator involved in many cytokine induced immune and inflammatory responses. This gene along with interleukin 1 receptor, type II (IL1R2), interleukin 1 receptor-like 2 (IL1RL2), and interleukin 1 receptor-like 1 (IL1RL1) form a cytokine receptor gene cluster in a region mapped to chromosome 2q12.
General function
Receptor
Comment
The interleukin-1 system mediates inflammation and immunity, and is activated by macrophages, keratinocytes, stimulated B lymphocytes, and fibroblasts.
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), 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). Also, Hogquist et al. (1991) demonstrated that both interleukin-1 a and b are involved in apoptosis (cell death).
Expression regulated by
FSH, LH, Growth Factors/ cytokines, IGF-1
Comment
The relative amount of ovarian IL-1R(1) transcripts increased after administration of hCG to pregnant mare serum gonadotropin-primed immature rats. (Scherzer et al. 1996). Molecular probing of whole ovarian material in the course of a simulated estrous cycle revealed a progressive preovulatory increase in IL-1beta and type I IL-1R transcripts to an in vivo peak at the time of ovulation (Kol et al., 1999).
Also, Kol et al. (1997) found that treatment of whole ovarian dispersates from immature rats with IGF-I resulted in a decrease in type I IL-1R transcripts (an effect which was reversed by co-treatment with IL-1beta), suggesting that IGF-I may down-regulate ovarian IL-1 action by decreasing type I IL-1R gene expression.
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. Just before follicular rupture, IL-R t1 staining was observed in cumulus and granulosa cells. After ovulation, IL-1a and IL-1b, and IL-1R tI were found in the granulosa-luteal cells of the developing corpus luteum.
From in situ hybridization studies on rat ovaries, IL-1b and IL-1R tI transcripts were localized to the granulosa cells, innermost layers of the theca interna, and oocyte of the untreated immature ovary. (Kol et al., 1999)
In humans, the IL-1 system as been localized to granulosa cells, luteal cells, ovarian surface epithelium, whole ovary, and follicular fluid (Terranova, 1997).
Follicle stages
Antral, Preovulatory, Corpus luteum
Comment
IL-1R tI localized identified in ovary (during follicular development and ovulation) and the developing corpus luteum (see "Ovarian cell type" comments).
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Phenotypes
Mutations
2 mutations
Species: mouse
Mutation name: IL-1R t1
type: null mutation fertility: fertile Comment: Mice lacking type I IL-1 receptors are of normal vigor and exhibit no overt phenotype. B cells from type I IL-1R-/- mice activated in vitro with anti-IgM do not proliferate in response to IL-1, but do so in response to IL-4. Injection of murine IL-1alpha does not induce detectable serum IL-6 levels in type I IL-1R-/- mice, but equivalent levels are produced in response to LPS. Type I IL-1R-/- mice have normal serum Ig levels and generate equivalent primary and secondary Ab responses as wild-type mice. In response to LPS, acute phase protein mRNA induction are equivalent in type I IL-1R-/- and wild-type mice. Type I IL-1R-/- mice do not differ from control mice in susceptibility to either a lethal challenge with d-galactosamine plus LPS or high dose LPS. Interestingly, ICE-/-/type I IL-1R-/- double mutant mice are resistant to high dose LPS. Type I IL-1R-/- mice backcrossed to the C57BL/6 background were as equally resistant as wild-type mice to Listeria monocytogenes (Glaccum 1997).
Species: mouse
Mutation name: IL-1R t1
type: null mutation fertility: fertile Comment:Abbondanzo et al. (1996) analyzed the reproduction of mice deficient for the IL-1Rt1. Besides having a smaller mean litter size, these mice did not show major changes in their reproduction.