NCBI Summary:
This antimicrobial gene belongs to the subfamily of small cytokine CC genes. Cytokines are a family of secreted proteins involved in immunoregulatory and inflammatory processes. The CC cytokines are proteins characterized by two adjacent cysteines. The protein encoded by this gene displays chemotactic activity for lymphocytes and can repress proliferation of myeloid progenitors. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2014]
General function
Ligand, Cytokine
Comment
Cellular localization
Secreted
Comment
Ovarian function
Ovulation
Comment
Chemokine Ligand 20: A signal for leukocyte recruitment during human ovulation? Al-Alem L et al. (2015) Ovulation is one of the cornerstones of female fertility. Disruption of the ovulatory process results in infertility, which affects approximately 10 of couples. Utilizing a unique model where the dominant follicle is collected across the periovulatory period in women, we have identified a leukocyte chemoattractant, chemokine ligand 20 (CCL20) in the human ovary. CCL20 mRNA is massively induced after an in vivo hCG stimulus in granulosa (>10,000 fold) and theca (>4,000 fold) cells collected during the early ovulatory (12-18h) and late ovulatory (18-34h) periods after hCG administration. As the LH surge sets in motion an inflammatory reaction characterized by an influx of leukocytes and CCL20 is known to recruit leukocytes in other systems, the composition of ovarian leukocytes (CD45+) containing the CCL20 receptor CCR6 was determined immediately prior to ovulation. CD45+/CCR6+ cells were primarily natural killer-cells (41%) along with B-cells (12%), T-cells (11%), neutrophils (10%), and monocytes (9%). Importantly, exogenous CCL20 stimulated ovarian leukocyte migration 59% within 90 minutes. Due to the difficulties in obtaining human follicles, an in vitro model was developed using granulosa-lutein cells (GLC) to explore CCL20 regulation. CCL20 expression increased 40-fold within 6h after hCG, was regulated partially by the EGF pathway, and was positively correlated with progesterone production. These results demonstrate that hCG dramatically increases CCL20 expression in the human ovary, that ovarian leukocytes contain the CCL20 receptor, and that CCL20 stimulates leukocyte migration. Our findings raise the prospect that CCL20 may aid in the final ovulatory events and contribute to fertility in women.//////////////////
Expression regulated by
LH, Growth Factors/ cytokines
Comment
Ovarian localization
Oocyte, Granulosa
Comment
CCL20-CCR6 axis directs sperm-oocyte interaction and its dysregulation correlates/associates with male infertility. Duan YG et al. (2020) The interaction of sperm with the oocyte is pivotal during the process of mammalian fertilization. The limited numbers of sperm that reach the fallopian tube as well as anatomic restrictions indicate that human sperm-oocyte encounter is not a matter of chance but a directed process. Chemotaxis is the proposed mechanism for re-orientating sperm towards the source of a chemoattractant, and hence to the oocyte. Chemokines represent a superfamily of small (8-11 kDa), cytokine-like proteins that have been shown to mediate chemotaxis and tissue-specific homing of leukocytes through binding to specific chemokine receptors such as CCRs. Here we show that CCR6 is abundantly expressed on human sperms and in human testes. Furthermore, radioligand-binding experiments showed that CCL20 bound human sperm in a specific manner. Conversely, granulosa cells of the oocyte-surrounding cumulus complex as well as human oocytes represent an abundant source of the CCR6-specific ligand CCL20. In human ovaries, CCL20 shows a cycle-dependent expression pattern with peak expression in the preovulatory phase and CCL20 protein induces chemotactic responses of human sperm. Neutralization of CCL20 in ovarian follicular fluid significantly impairs sperm migratory responses. Conversely, analyses in infertile men with inflammatory conditions of the reproductive organs demonstrate a significant increase of CCL20/CCR6 expression in testis and ejaculate. Taken together, findings of the present study suggest that CCR6-CCL20 interaction may represent an important factor in directing sperm-oocyte interaction.//////////////////
Production of macrophage inflammatory protein-3alpha in human follicular fluid and cultured granulosa cells.
Kawano Y, et al 2004 .
OBJECTIVE: To investigate the role of macrophageinflammatory protein (MIP)-3alpha in human ovulation. DESIGN: Study of the levels of MIP-3alpha in serum and follicular fluid. The effects of interleukin (IL)-1alpha, IL-1 receptor antagonist (RA), and tumor necrosis factor (TNF)-alpha on the secretion of MIP-3alpha by primary cultured granulosa-lutein cells and an immortalized granulosa cell line (GC1a) were investigated. SETTING: Research laboratory at a university medical school. PATIENT(S): Forty-six patients with sterility undergoing in vitro fertilization and embryo transfer (IVF-ET). INTERVENTION(S): Follicular fluid was obtained from study participants, and granulosa-lutein cells and GC1a were incubated with IL-1alpha, IL-1RA, or TNF-alpha for 4 to 32 hours. MAIN OUTCOME MEASURE(S): The concentration of MIP-3alpha in human follicular fluid was measured and correlated with oocyte maturation. We also cultured granulosa cells and examined the regulation of MIP-3alpha production. The concentrations of MIP-3alpha in the serum, follicular fluid, and culture medium were measured using enzyme-linked immunoabsorbent assay. RESULT(S): Concentrations of MIP-3alpha were significantly higher in the follicular fluid, but it was not detected in the serum. Concentrations of MIP-3alpha were statistically significantly higher in the follicular fluid containing mature oocytes than in follicular fluid containing immature oocytes. The production of MIP-3alpha was markedly increased over the basal level after treatment with IL-1alpha and TNF-alpha in a dose-dependent manner. The stimulatory effect of IL-1alpha was inhibited by IL-1RA. CONCLUSION(S): Our data suggest that MIP-3alpha was present in follicular fluid and correlated with oocyte maturation, and was regulated by IL-1alpha and TNF-alpha. Thus, MIP-3alpha may play an important role in the human preovulatory process.