The polypeptide
chain of human fractalkine was predicted to be part of a 373-amino acid protein that carries the chemokine domain on
top of an extended mucin-like stalk. This molecule can exist in 2 forms: as membrane-anchored or as a shed 95-kD
glycoprotein. The soluble fractalkine has potent chemoattractant activity for T cells and monocytes, and the cell
surface-bound protein, which is induced on activated primary endothelial cells, promotes strong adhesion of those
leukocytes.
NCBI Summary:
This gene belongs to the CX3C subgroup of chemokines, characterized by the number of amino acids located between the conserved cysteine residues. This is the only member of the CX3C subgroup, which contains three amino acids between cysteine residues, resulting in a Cys-X-X-X-Cys configuration. The encoded protein contains an extended mucin-like stalk with a chemokine domain on top, and exists in both a membrane-anchored form where it acts as a binding molecule, or, in soluble form, as a chemotactic cytokine. The mature form of this protein can be cleaved at the cell surface, yielding different soluble forms that can interact with the G-protein coupled receptor, C-X3-C motif chemokine receptor 1 gene product. This gene plays a role in a wide range of diseases, including cancer, vasculitis, neuropathies, atherosclerosis, inflammatory diseases, and in human immunodeficiency virus infections. [provided by RefSeq, Sep 2017]
General function
Ligand, Cytokine
Comment
Cellular localization
Secreted, Plasma membrane
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Ovarian function
Ovulation, Steroid metabolism, Luteinization
Comment
Fractalkine restores the decreased expression of StAR and progesterone in granulosa cells from patients with polycystic ovary syndrome. Huang S et al. (2016) Low progesterone levels are associated with luteal phase deficiency in women with polycystic ovary syndrome (PCOS). The mechanisms regulating progesterone biosynthesis in the granulosa cells from women with PCOS is largely unknown. Fractalkine is expressed in human ovaries, and is reported to regulate progesterone production in granulosa cells of healthy women. In the current study, we aimed to examine the role of fractalkine in women with PCOS. Reduced fractalkine levels were found in follicular fluid and granulosa cells, accompanied by decreased progesterone production and reduced steroidogenic acute regulatory protein (StAR) expression in the granulosa cells of patients with PCOS. Administration of fractalkine reversed the inhibition of progesterone and StAR expression. The mechanism mediating these effects may be associated with the inhibition of ERK activity in the granulosa cells from women with PCOS. Our findings revealed that fractalkine regulated steroidogenesis in follicular granulosa cells of women with PCOS.//////////////////
Fractalkine is expressed in the human ovary and increases progesterone biosynthesis in human luteinised granulosa cells. Huang S et al. ABSTRACT: BACKGROUND: Recent evidence from rodent ovaries has demonstrated expression of fractalkine and the existence of fractalkine receptor, and showed that there is a significant increase in steroidogenesis in response to fractalkine, yet the role of fractalkine and CX3CR1 in the human ovary is still unknown. This study aimed to determine the expression levels of fractalkine and CX3CR1 in the human ovary and to investigate their roles in sexual hormone biosynthesis by human luteinising granulosa cells. This is the first detailed report of fractalkine and CX3CR1 expression and function in the human ovary. METHODS: Fractalkine and CX3CR1 expression levels were measured by immunohistochemistry using ovarian tissue from pathological specimens from five individuals. Granulosa cells were obtained from patients during IVF treatment. They were cultured and treated with increasing doses of hCG with or without fractalkine. Media were collected to detect estradiol and progesterone by chemiluminescence. StAR, 3-betaHSD and CYP11A expression were determined in granulosa cells treated with or without fractalkine by real-time RT-PCR. RESULTS: Fractalkine and CX3CR1 were expressed in the human ovary and in luteinising granulosa cells. However, fractalkine expression was stronger in luteinising granulosa cells. Treatment with fractalkine augmented hCG stimulation of progesterone production in a dose-dependent manner with concomitant increases in transcript levels for key steroidogenic enzymes (StAR, 3-betaHSD and CYP11A) but had no effect on estradiol biosynthesis(P less than 0.05). CONCLUSIONS: Fractalkine and CX3CR1 were found to express in human ovary and luteinising granulosa cells. Fractalkine can increase the biosynthesis of progesterone in a dose-dependent manner by enhancing transcript levels of key steroidogenic enzymes.
Kenneth H. H. Wong et al 2002 reported the expression, Hormonal Regulation, and Cyclic Variation of
Chemokines in the Rat Ovary.
A growing body of evidence suggests that mammalian ovulation bears similarities to local inflammatory reactions.
Monocytes/macrophages, eosinophils, and neutrophils are known to infiltrate the area surrounding the dominant follicle
before ovulation. Candidate local chemoattractants may include a family of small cytokines, also known as chemokines. In
the present study, quantitative RT-PCR was used to initially identify and quantify the chemokines expressed in the
preovulatory rat ovary. The chemokines monocyte chemotatic protein 1 (MCP-1), MCP-3, macrophage inflammatory protein
1 (MIP-1), MIP-1? MIP-1, regulated upon activation normal T cell expressed and secreted, eotaxin, interferon-inducible
protein of 10 kDa, growth-regulated oncogene, lymphotactin, and fractalkine were all expressed in the PMSG-primed rat
ovary 6 h post human CG. The cyclic variation of the ovary-positive chemokines was also evaluated throughout the course of a superovulated ovarian
cycle. Significant preovulatory up-regulation relative to the untreated control state was documented for MCP-1 (18-fold), MCP-3 (12-fold), and growth-regulated oncogene (25-fold). In contrast, the preovulatory ovarian expression of eotaxin, fractalkine and regulated upon activation normal T cell expressed and secreted was not increased. These observations
suggest that intraovarian chemokines may be responsible for the cyclic intraovarian residence of representatives of the white
blood cell series.
Gonadotropin stimulation of ovarian fractalkine expression and fractalkine augmentation of progesterone biosynthesis by luteinizing granulosa cells. Zhao P et al. Recent studies indicated that ovarian functions are regulated by diverse paracrine factors induced by the preovulatory increases in circulating LH. Based on DNA microarray analyses and real-time RT-PCR, we found a major increase in the transcript levels of a chemokine fractalkine following hCG treatment during the preovulatory period in gonadotropin-primed immature mice and rats. Although CX3CR1, the seven transmembrane receptor for fractalkine, was also found in murine ovaries, its transcripts displayed minimal changes. Using tandem RT-PCR and immunohistochemistry, fractalkine transcripts and proteins were localized in cumulus, mural granulosa, and theca cells as well as the oocytes whereas CX3CR1 was found in the same cells except the oocyte. Real-time RT-PCR further indicated the hCG induction of fractalkine transcripts in different ovarian compartments, with the highest increases found in granulosa cells. In cultured granulosa cells, treatment with fractalkine augmented hCG stimulation of progesterone, but not estradiol and cAMP biosynthesis with concomitant increases in transcript levels for key steroidogenic enzymes (StAR, CYP11A, and 3-beta hydroxysteroid dehydrogenase). In cultured preovulatory follicles, treatment with fractalkine also augmented progesterone production stimulated by hCG. Furthermore, treatment with fractalkine augmented the phosphorylation of P38 mitogen-activated protein kinase in cultured granulosa cells. The present data demonstrated that increases in preovulatory LH/hCG induce the expression of fractalkine to augment the luteinization of preovulatory granulosa cells and suggest the fractalkine/CX3CR1 signaling system plays a potential paracrine/autocrine role in preovulatory follicles.
Expression regulated by
LH
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Ovarian localization
Granulosa
Comment
Fractalkine and apoptotic/anti-apoptotic markers in granulosa cells of women with polycystic ovarian syndrome. Raei Sadigh A et al. (2020) Owing to the role of fractalkine in regulating cellular apoptosis/proliferation, we investigated fractalkine effects on apoptosis/proliferation signaling of granulosa cells in polycystic ovarian syndrome (PCOS) patients through in vitro and in vivo experiments. In vivo, granulosa cells were collected from 40 women undergoing oocyte retrieval (20 controls and 20 PCOS). The expression levels of fractalkine, BAX, Bcl2, Bcl2-XL, Bad, and TNF-α were assessed using RT-PCR. In vitro, we determined the effect of different doses of fractalkine on the expression of the above mentioned genes in GCs of both groups. We found that the expression levels of fractalkine and Bcl-2 were significantly lower in the GCs of PCOS patients compared to the control group (p < 0.05). In contrast, the expression levels of TNF-α and BAX were higher in the patient's group than in the control group. The results suggested that expression levels of fractalkine were negatively and positively correlated with the number of oocytes and fertilized oocytes respectively. Moreover, fractalkine could dose-dependently increase fractalkine and decrease BAD, BAX, Bcl-xl, and TNF-α expressions in the control GCs. In contrast, GCs collected from PCOS patients revealed an increase in expression of BAD, BAX, and Bcl-xl following fractalkine treatment. Our findings indicated that insufficient expression of fractalkine in PCOS patients is related with elevated apoptotic and inflammatory markers and reduced anti-apoptotic genes in the GCs.//////////////////