| interleukin 1 beta | OKDB#: 304 |
| Symbols: | IL1B | Species: | human | ||
| Synonyms: | IL-1, IL1F2, IL1beta, IL1-BETA | Locus: | 2q14.1 in Homo sapiens |
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| General Comment |
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).///////involved in pyroptosis
NCBI Summary: The protein encoded by this gene is a member of the interleukin 1 cytokine family. This cytokine is produced by activated macrophages as a proprotein, which is proteolytically processed to its active form by caspase 1 (CASP1/ICE). This cytokine is an important mediator of the inflammatory response, and is involved in a variety of cellular activities, including cell proliferation, differentiation, and apoptosis. The induction of cyclooxygenase-2 (PTGS2/COX2) by this cytokine in the central nervous system (CNS) is found to contribute to inflammatory pain hypersensitivity. Similarly, IL-1B has been implicated in human osteoarthritis pathogenesis. Patients with severe Coronavirus Disease 2019 (COVID-19) present elevated levels of pro-inflammatory cytokines such as IL-1B in bronchial alveolar lavage fluid samples. The lung damage induced by the Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is to a large extent, a result of the inflammatory response promoted by cytokines such as IL-1B. This gene and eight other interleukin 1 family genes form a cytokine gene cluster on chromosome 2. [provided by RefSeq, Jul 2020] |
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| General function | Ligand, Cytokine, Cell death/survival, Apoptosis | ||||
| Comment | IL-1-a and IL-1b are synthesized by a variety of cell types including activated macrophages, keratinocytes, stimulated B lymphocytes, and fibroblasts, and are potent mediators of inflammation and immunity. | ||||
| Cellular localization | Secreted | ||||
| Comment | |||||
| Ovarian function | Follicle development, Initiation of primordial follicle growth, Antral follicle growth, Follicle atresia, Ovulation, Steroid metabolism, Luteinization, Early embryo development | ||||
| Comment | IL-1β up-regulates StAR and progesterone production through the ERK1/2 and p38-mediated CREB signaling pathways in human granulosa-lutein cells. Dang X et al. (2017) The pro-inflammatory cytokine interleukin-1β (IL-1β) may be involved in several ovulation-associated events, such as proteases synthesis, prostaglandin production and steroidogenesis in granulosa cells. However, the exact effect of IL-1β on progesterone synthesis in granulosa cells and the underlying mechanism remain unclear. By using cultured granulosa-lutein cells collected from women undergoing in vitro fertilization or intracytoplasmic sperm injection, we found that IL-1β up-regulated steroidogenic acute regulatory protein (StAR) expression and progesterone synthesis in granulosa-lutein cells, which was comparable with luteinizing hormone (LH) effect and could be abolished by an IL-1 receptor antagonist. Moreover, IL-1β activated the phosphorylation of cAMP response element-binding protein (CREB) and knock-down of CREB attenuated the induction of StAR expression and progesterone synthesis by IL-1β in granulosa-lutein cells. Furthermore, IL-1β activated the ERK1/2 and p38 pathways and inhibition of the ERK1/2 and p38 pathways attenuated the IL-1β-induced phosphorylation of CREB, StAR expression and progesterone synthesis in granulosa-lutein cells. In conclusion, IL-1β could up-regulate StAR expression and stimulate progesterone biosynthesis through increase in CREB phosphorylation via activating the ERK1/2 and p38 pathways in human granulosa-lutein cells.////////////////// Protein and messenger RNA expression of interleukin 1 system members in bovine ovarian follicles and effects of interleukin 1β on primordial follicle activation and survival in vitro. Passos JR et al. (2015) This study aimed to investigate the expression of interleukin 1 (IL-1) system members (proteins and messenger RNA of ligands and receptors) and its distribution in ovarian follicles of cyclic cows and to evaluate the effects of IL-1β on the survival and activation of primordial follicles in vitro. The ovaries were processed for localization of IL-1 system in preantral and antral follicles by immunohistochemical, real-time polymerase chain reaction, and Western blot analysis. For in vitro studies, ovarian fragments were cultured in α-MEM(+) supplemented with IL-1β (0, 1, 10, 50, or 100 ng/mL), and after 6 d, the cultured tissues were processed for histologic analysis. Immunohistochemical results showed that the IL-1 system proteins IL-1β, IL-1RA, IL-1RI, and IL-1RII were detected in the cytoplasm of oocytes and granulosa cells from all follicular categories and theca cells of antral follicles. Variable levels of messenger RNA for the IL-1 system members were observed at different stages of development. After 6 d of culture, the presence of IL-1β (10 or 50 ng/mL) was effective in maintaining the percentage of normal follicles and in promoting primordial follicle activation. In conclusion, IL-1 system members are differentially expressed in ovarian follicles according to their stage of development. Moreover, IL-1β promotes the development of primordial follicles. These results indicate an important role of the IL-1 system in the regulation of bovine folliculogenesis.////////////////// Good fertilization results associated with high IL-1beta concentrations in follicular fluid of IVF patients. Zollner KP 2014 et al. OBJECTIVE To determine the levels of interleukin-1 beta (IL-1beta) in follicular fluid and embryo culture fluid after controlled ovarian hyperstimulation and to assess the association of this cytokine with the outcome of in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) treatment and embryo transfer. STUDY DESIGN A total of 256 couples undergoing the IVF/ICSI program were included in this prospective study. Zygote quality, embryo and blastocyst morphology were evaluated, and embryo transfer was performed 5 days after oocyte recovery. IL-1beta concentrations were measured in follicular fluid and embryo culture fluid of the third and fifth culture days. RESULTS Embryo replacement was performed with a median of 2 embryos per cycle. In all, 44 clinical pregnancies were achieved in 256 assisted reproductive technology (ART) cycles (pregnancy rate: 19.8% per transfer). Follicular fluid concentrations of IL-1P were not significantly different in pregnant (2.1 pg/mL) and nonpregnant women (2.7 pg/mL). Follicular fluid of lVF, but not ICSI, patients with good fertilization rates (> 90%) contained significantly higher levels of IL-1beta (3.3 pg/ mL) than did follicular fluid of women with fertilization rates < or = 90% (2.0 pg/mL, p < 0.05). No correlation was found between intrafollicular IL-1beta and zygote morphology, day 3 and day 5 embryo morphology. There was no relationship between IL-1beta in culture fluid supernatants and embryonic development. CONCLUSION In IVF patients high levels of intrafollicular IL-1beta were associated with good fertilization rates. There seems to be no correlation between IL-1beta concentrations in follicular fluid or embryo culture fluid and embryo morphology or pregnancy outcome of ART cycles. ///////////////////////// Role of interleukin-1?in the regulation of porcine corpora lutea during the late luteal phase of the cycle and during pregnancy. Zmijewska A et al. Interleukin-1?(IL-1? may regulate ovarian physiology. In this study, the influence of IL-1?on secretory activity within the corpora lutea (CL) of cyclic and gravid pigs was determined in vitro during different stages of the CL lifespan, e.g. on Days 10-11, 12-13 and 15-16 of the oestrous cycle and pregnancy. IL-1?(10 ng/ml) increased prostaglandin E2 (PGE2) secretion from CL of the cyclic and gravid pigs during studied days of the oestrous cycle and pregnancy. Increase (P < 0.05) of prostaglandin F2a (PGF2a) in IL-1?treated CL was demonstrated only on Days 10-11 of the oestrous cycle. More potent stimulatory effect of IL-1?on PGE2 than PGF2a secretion resulted in the enhancement of the PGE2:PGF2a ratio in cyclic and early pregnant CL. IL-1?increased (P < 0.05) progesterone (P4) secretion only in gravid CL and had no effect on oestradiol-17?(E2) release. Expression of cyclooxygenase-2 (COX-2) mRNA was stimulated (P < 0.05) in IL-1?treated cyclic and gravid CL. Expression of prostaglandin synthase mRNAs in response to IL-1?did not increase. In conclusion, IL-1?modulates PGE2, PGF2a and P4 secretion from porcine CL, depending on luteal stage and the surrounding hormonal milieu. The cytokine may act locally in porcine CL for luteotrophic support throughout the PGE2-mediated synthesis and secretion. 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). Hogquist et al. (1991) demonstrated that both interleukin-1 a and b are involved in apoptosis (cell death). Chun et al.(1995) showed that IL-1 beta suppresses apoptosis in rat ovarian follicles by increasing nitric oxide production. (1995). Ben-Shlomo et al. (1997) found that IL-1beta increases glucose uptake and induces glycolysis in aerobically cultured rat ovarian cells, suggesting that IL-1beta may mediate the gonadotropin-induced midcycle metabolic shift. 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 | ||||
| Expression regulated by | FSH, LH, Growth Factors/ cytokines, IL-8, IL-1 receptor antagonist, GM-CSF | ||||
| Comment | In gonadotropin-stimulated immature rat ovaries, IL-1b expression was detected in theca and increases in expression were observed after treatment with hCG (Hurwitz et al., 1991). Regulation (gene expression, availability, and modulatory factors) of IL-1b reviewed in Watkins et al. (1999). Ujioka et al. (1999) studied cytokine interaction among interleukin-1 beta, interleukin-8, and interleukin-1 receptor antagonist in the rabbit. Administration of anti-IL-8 antiserum reduced the accumulation of IL-1 beta, and anti-IL-1 receptor antagonist antiserum significantly augmented the accumulation of IL-1 beta. Tamura et al. (1999) found that granulocyte-macrophage colony-stimulating factor (GM-CSF) enhances interleukin-1beta stimulated histamine release in the preovulatory rat ovary. | ||||
| Ovarian localization | Oocyte, Granulosa, Theca, Luteal cells, Surface epithelium | ||||
| 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. 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 gonadotropin-stimulated immature rat ovaries, Hurwitz et al. (1991) detected IL-1b expression in theca; expression increased after human chorionic gonadotropin (hCG) treatment. 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. In humans, the IL-1 system as been localized to granulosa cells, luteal cells, ovarian surface epithelium, whole ovary, and follicular fluid (Terranova, 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. | ||||
| Follicle stages | Antral, Preovulatory, Corpus luteum | ||||
| Comment | The interleukin-1?system in the corpora lutea of pigs during early pregnancy and the estrous cycle. Zmijewska A et al. Expression of mRNAs encoding interleukin-1?(IL-1?, IL-1?receptor I (IL-1RI), IL-1 receptor accessory protein (IL-1RAcP) and IL-1 receptor antagonist (IL-1Ra), as well as synthesis of IL-1?and IL-1RI proteins, were examined in the corpus luteum (CL) during critical stages of CL activity on days 10-16 of pregnancy and 2-16 of the estrous cycle. Luteal cells were cultured in vitro with IL-1? and the effect on release of steroid hormones was determined. Expression of the IL-1?system in the CL changed significantly during pregnancy and the estrous cycle. IL-1? IL-1RI, and IL-1Ra mRNA levels were elevated on days 12-13, whereas IL-1RAcP mRNA was increased on days 15-16 of pregnancy. In cyclic CL, expression of IL-1? IL-1RI, and IL-1RAcP mRNAs was increased on days 12-13. IL-1?and IL-1RI protein were highest in the CL on days 10-11 and 8-11 of pregnancy and the estrous cycle. Luteal cells harvested from gravid and cyclic CL produced IL-1?in vitro. IL-1?increased progesterone and estradiol-17?(E2) release by luteal cells on days 10-16 and 10-11 of pregnancy, respectively and on days 2-11 of the estrous cycle. IL-1?decreased the level of E2 produced by regressed CL (days 15-16). Expression of the IL-1?system in CL and IL-1?secretion from luteal cells changed depending on the status of the CL. These data show that IL-1?may be involved in intraluteal, luteotrophic regulation of CL functions in gravid and cyclic pigs. | ||||
| Phenotypes |
PCO (polycystic ovarian syndrome) |
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| Mutations |
4 mutations
Species: human
Species: human
Species: mouse
Species: mouse
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| Genomic Region | show genomic region | ||||
| Phenotypes and GWAS | show phenotypes and GWAS | ||||
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| created: | Dec. 5, 1999, midnight | by: |
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| last update: | Sept. 28, 2020, 11:55 a.m. | by: | hsueh email: |
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