This gene encodes a SASP.
Interleukin-8, otherwise known as neutrophil-activating peptide-1, is a tissue-derived peptide secreted by several types of cells in response to inflammatory stimuli. Modi et al. (1990) cloned the IL8 gene and mapped it to 4q12-q21 by somatic cell hybridization and in situ hybridization. Modi et al. (1990) pointed out that this is the same chromosome location as that of 3 other members of the platelet factor-4 gene superfamily: platelet factor-4, melanoma growth stimulatory activity, and interferon-gamma-induced factor.
IL-8, like the IL-1 system (including IL-1a, IL-1b, IL-1 receptor antagonist, and IL-1 receptors type I and II), has been identified in the ovaries of several species (Terranova 1997) and is enhanced by the stimulation of gonadotropin (Runesson, 1996). IL-8 and the IL-1 system are thought to have related functions in the ovulatory process.
NCBI Summary:
The protein encoded by this gene is a member of the CXC chemokine family and is a major mediator of the inflammatory response. The encoded protein is secreted primarily by neutrophils, where it serves as a chemotactic factor by guiding the neutrophils to the site of infection. This chemokine is also a potent angiogenic factor. This gene is believed to play a role in the pathogenesis of bronchiolitis, a common respiratory tract disease caused by viral infection. This gene and other members of the CXC chemokine gene family form a gene cluster in a region of chromosome 4q. [provided by RefSeq, Aug 2017]
General function
Hormone
Comment
Interleukin-8, otherwise known as neutrophil-activating peptide-1, is a tissue-derived peptide secreted by several types of cells in response to inflammatory stimuli
(Modi et al. (1990).
Cellular localization
Secreted
Comment
Ovarian function
Follicle development, Antral follicle growth, Follicle atresia, Ovulation, Steroid metabolism, Luteinization, Early embryo development
Comment
Human granulosa-luteal cells initiate an innate immune response to pathogen-associated molecules. Ibrahim LA et al. (2016) The microenvironment of the ovarian follicle is key to the developmental success of the oocyte. Minor changes within the follicular microenvironment can significantly disrupt oocyte development, compromising the formation of competent embryos and reducing fertility. Previously described as a sterile environment, the ovarian follicle of women has been shown to contain colonizing bacterial strains, whereas in domestic species, pathogen-associated molecules are concentrated in the follicular fluid of animals with uterine infection. The aim of this study is to determine whether human granulosa-luteal cells mount an innate immune response to pathogen-associated molecules, potentially disrupting the microenvironment of the ovarian follicle. Human granulosa-luteal cells were collected from patients undergoing assisted reproduction. Cells were cultured in the presence of pathogen-associated molecules (LPS, FSL-1 and Pam3CSK4) for 24h. Supernatants and total RNA were collected for assessment by PCR and ELISA. Granulosa-luteal cells were shown to express the molecular machinery required to respond to a range of pathogen-associated molecules. Expression of TLR4 varied up to 15-fold between individual patients. Granulosa-luteal cells increased the expression of the inflammatory mediators IL1B, IL6 and CXCL8 in the presence of the TLR4 agonist E. coli LPS. Similarly, the TLR2/6 ligand, FSL-1, increased the expression of IL6 and CXCL8. Although no detectable changes in CYP19A1 or STAR expression were observed in granulosa-luteal cells following challenge, a significant reduction in progesterone secretion was measured after treatment with FSL-1. These findings demonstrate the ability of human granulosa-luteal cells to respond to pathogen-associated molecules and generate an innate immune response.//////////////////
Intrafollicular interleukin-8, interleukin-12, and adrenomedullin are the promising prognostic markers of oocyte and embryo quality in women with endometriosis. Singh AK et al. (2016) The study aimed to investigate key intrafollicular prognostic factors among various cytokines and angiogenic molecules for prediction of mature oocytes and good-quality embryos in women with endometriosis undergoing in vitro fertilization (IVF). Paired follicular fluid and serum samples were collected from 200 women with advanced stage endometriosis and 140 normal ovulating women during oocyte retrieval. The concentrations of cytokines (pro-inflammatory: IL-1β, TNF-α, IL-2, IL-8, IL-12, IFN-γ; anti-inflammatory: IL-4, IL-6, IL-10) and angiogenic molecules (vascular endothelial growth factor (VEGF), adrenomedullin, angiogenin) were determined in follicular fluid and serum using ELISA. Expression of these molecules was subjected to multivariate analysis for the identification of major predictive markers of oocyte and embryo quality. Receiver operating characteristic (ROC) curve was applied to determine the best cutoff point for the discrimination between mature and immature oocytes in these women. Significant increases in levels of cytokines and angiogenic molecules were observed in women with endometriosis compared to controls (P < 0.001). From the validated partial least squares-discriminant analysis (PLS-DA) model, IL-8, IL-12, and adrenomedullin were identified as the most important factors contributing to endometriosis and were negatively associated with oocyte maturity and embryo quality. The levels of IL-8, IL-12, and adrenomedullin may be good indicators of embryo and oocyte quality in endometriosis patients undergoing IVF. Further studies are necessary to ascertain the potential of these markers for oocyte and embryo developmental competence which may help improve the chances of a successful IVF in endometriosis patients.//////////////////
Effects of IL8 and Immune Cells on the Regulation of Luteal Progesterone Secretion. Talbott H 2014 et al.
Recent studies suggest that chemokines may mediate the luteolytic action of PGF2a (PGF). Our objective was to identify chemokines induced by PGF in vivo and to determine the effects of IL8 on specific luteal cell types in vitro. Midcycle cows were injected with saline or PGF, ovaries were removed after 0.5 - 4 h and chemokine expression was analyzed by qPCR. In vitro expression of IL8 was analyzed after PGF administration and with cell signaling inhibitors to determine the mechanism of PGF-induced chemokine expression. Purified neutrophils were analyzed for migration and activation in response to IL8 and PGF. Purified luteal cell types (steroidogenic, endothelial and fibroblast cells) were used to identify which cells respond to chemokines. Neutrophils and peripheral blood mononuclear cells (PBMCs) were co-cultured with steroidogenic cells to determine their effect on progesterone production. IL8, CXCL2, CCL2, and CCL8 transcripts were rapidly increased following PGF treatment in vivo and. The stimulatory of PGF on IL8 mRNA expression in vitro was prevented by inhibition of p38 and JNK signaling. IL8, but not PGF, TNF, or TGFB1, stimulated neutrophil migration. IL8 had no apparent action in purified luteal steroidogenic, endothelial, or fibroblast cells, but IL8 stimulated ERK phosphorylation in neutrophils. In co-culture experiments neither IL8 nor activated neutrophils altered basal or LH-stimulated luteal cell progesterone synthesis. In contrast, activated PBMCs inhibited LH-stimulated progesterone synthesis from cultured luteal cells. These data implicate a complex cascade of events during luteolysis involving chemokine signaling, neutrophil recruitment, and immune cell action within the corpus luteum.
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Interleukin-8 stimulates progesterone production via the MEK pathway in ovarian theca cells. Shimizu T et al. Interleukin 8 (IL-8) is a chemoattractant associated with ovulation in the mammalian ovary. This chemokine is also involved in the recruitment and activation of neutrophils. Using bovine tissue, we examined the possible role of IL-8 in steroid production by theca cells of the large ovarian follicles. IL-8 promoted progesterone production and stimulated StAR expression in cultured theca cells. The inhibitor of p38 did not disturb the P4 production and StAR expression in IL-8-treated theca cells. On the other hand, the inhibitor of MEK disturbed the P4 production and expression of StAR in theca cells treated with IL-8. These results suggest that IL-8 is associated with progesterone production in bovine theca cells via the MEK pathway.
Effects of interleukin-8 on estradiol and progesterone production by bovine granulosa cells from large follicles and progesterone production by luteinizing granulosa cells in culture. Shimizu T et al. Interleukin 8 (IL-8) is a chemoattractant involved in the recruitment and activation of neutrophils and is associated with the ovulate process. We examined the possible role of IL-8 in steroid production by bovine granulosa cells before and after ovulation. The concentration of IL-8 in the follicular fluid of estrogen-active dominant (EAD) and pre-ovulatory follicles (POF) was higher than that of small follicles (SF). CXCR1 mRNA expression was higher in the granulosa cells of EAD and POF than that of SF. In contrast, CXCR2 mRNA expression was lower in granulosa cells of EAD and POF than in SF. IL-8 inhibited estradiol (E2) production in follicle-stimulating hormone (FSH)-treated granulosa cells at 48h of culture. IL-8 also suppressed CYP19A1 mRNA expression in FSH-treated granulosa cells. IL-8 stimulated progesterone (P4) production in luteinizing hormone (LH)-treated granulosa cells at 48h of culture. Although IL-8 did not alter the expression of genes associated with P4 production, it induced StAR protein expression in LH-treated granulosa cells. The expression of CXCR1 mRNA in corpus luteum (CL) did not change during the luteal phase. In contrast, the expression of CXCR2 mRNA in middle CL was significantly higher than in early and regression CL during the luteal phase. In luteinizing granulosa cells, an in vitro model of granulosa cell luteinization, CXCR2 mRNA expression was downregulated, whereas CXCR1 mRNA expression was unchanged. IL-8 also stimulated P4 production in luteinizing granulosa cells. These data provide evidence that IL-8 functions not only as a chemokine, but also act as a regulator of steroid synthesis in granulosa cells to promote luteinization after ovulation.
In studying the neutrophil-interleukin-8 system in human folliculogenesis, Chang et al. (1998) concluded that neutrophils are present in the theca of developing antral follicles, increase in number during atresia, and are associated with expression of interleukin-8 in the follicle wall.
Ujioka et al. (1998) have found that interleukin-8 mediates the human chorionic gonadotropin-induced rabbit ovulatory process by inducing the accumulation and activation of neutrophils. Buscher et al. (1999) studied cytokines in the follicular fluid of stimulated and non-stimulated human ovaries, and concluded that IL-8 (along with IL-6 and IL-1 RA) is involved in peri-ovulatory cellular interactions.
Belayet HM et al 2000 reported that pharmacologic doses of interleukin 8 suppositories induce
follicular maturation in rabbits.
Experiments were conducted using suppositories
containing 100 ng, 200 ng, 400 ng IL-8, 500 mu l Witepsol-base (control),
human menopausal gonadotropin (im) and conjugate of fluorescein
isithiocyanate-abelled IL-8, The levels of IL-8 in ovarian fluid were also
measured. Histology of ovaries treated with 200 ng IL-8 showed large antral
follicles filled with follicular fluid. The theca layer was divided into an
interna and an externa with large extracellular spaces, The granulosa cells
were loosened and appeared to be detaching from the granulosa layer,
Fluorescein isithiocyanate-labelled IL-8 conjugate
was seen in the follicular wall and endometrium.
The Effects of Epidermal Growth Factor and Transforming Growth Factor-a on Secretion of Interleukin-8 and Growth-Regulated Oncogene-a in Human Granulosa-Lutein Cells. Kawano Y et al. Background: In order to investigate the roles of epidermal growth factor (EGF) and transforming growth factor (TGF)-a in ovulation, we studied the production of interleukin (IL)-8 and growth-regulated oncogene (GRO)-a in cultured human granulosa-lutein cells. Methods: Granulosa-lutein cells obtained from the follicular fluids of in vitro fertilization and embryo transfer patients were cultured and treated with EGF, TGF-a, tumor necrosis factor (TNF)-a or 12-O-tetradecanoylphorbol 13-acetate (TPA). An immortalized granulosa cell line (GC1a) was also cultured and treated with EGF, TGF-a or mitogen-activated protein kinase kinase inhibitor. The supernatants were collected, and IL-8 and GRO-a were measured by ELISA. Results: The levels of IL-8 and GRO-a were significantly increased after treatment with EGF, TGF-a, TNF-a and TPA by primary cultured granulosa-lutein cells. The levels of IL-8 and GRO-a were also significantly increased after treatment with EGF or TGF-a in a dose-dependent manner by GC1a. When GC1a was treated with EGF, TGF-a or U0126, the levels of IL-8 and GRO-a were significantly decreased. Conclusion: Our data indicate that the production of IL-8 and GRO-a is upregulated by EGF and TGF-a. It is suggested that EGF and TGF-a may play an important role in luteinization processes involving IL-8 and GRO-a production.
Lipopolysaccharide Initiates Inflammation in Bovine Granulosa Cells via the TLR4 Pathway and Perturbs Oocyte Meiotic Progression in Vitro. Bromfield JJ et al. Infections of the reproductive tract or mammary gland with Gram-negative bacteria perturb ovarian function, follicular growth, and fecundity in cattle. We hypothesized that lipopolysaccharide (LPS) from Gram-negative bacteria stimulates an inflammatory response by ovarian granulosa cells that is mediated by Toll-like receptor (TLR) 4. The present study tested the capacity of bovine ovarian granulosa cells to initiate an inflammatory response to pathogen-associated molecular patterns and determined subsequent effects on the in vitro maturation of oocytes. Granulosa cells elicited an inflammatory response to pathogen-associated molecular patterns (LPS, lipoteichoic acid, peptidoglycan, or Pam3CSK4) with accumulation of the cytokine IL-6, and the chemokine IL-8, in a time- and dose-dependent manner. Granulosa cells responded acutely to LPS with rapid phosphorylation of TLR signaling components, p38 and ERK, and increased expression of IL6 and IL8 mRNA, although nuclear translocation of p65 was not evident. Targeting TLR4 with small interfering RNA attenuated granulosa cell accumulation of IL-6 in response to LPS. Endocrine function of granulosa cells is regulated by FSH, but here, FSH also enhanced responsiveness to LPS, increasing IL-6 and IL-8 accumulation. Furthermore, LPS stimulated IL-6 secretion and expansion by cumulus-oocyte complexes and increased rates of meiotic arrest and germinal vesicle breakdown failure. In conclusion, bovine granulosa cells initiate an innate immune response to LPS via the TLR4 pathway, leading to inflammation and to perturbation of meiotic competence.
Effect of vascular endothelial growth factor (VEGF) on expressions of interleukin-8 (IL-8), IL-1ss and their receptors in bovine theca cells. Murayama C et al. Cytokines such as vascular endothelial growth factor (VEGF) and interleukins are involved in follicular development in the mammalian ovary. The aim of the present study is to examine the transcript of the IL-8 and IL-1 differs during follicular development and the relationships between IL-8, IL-1 and VEGF in the theca cells is still unknown. We first examined the gene expression of IL-8, IL-1ss, CXCR1, and IL-1R1 in the theca cells of pre-selection (PRF) and post-selection follicles (POF) from the bovine ovary. Expression of IL-8 and CXCR1 genes were observed in POF, whereas expression of IL-1ss and IL-1R1 genes was observed in both follicles. Secondary, we examined the effects of VEGF on the expression of IL-8, IL-1ss and their receptors genes in cultured bovine theca cells. Messenger RNA (mRNA) expression was quantified by using real-time PCR methods. VEGF stimulate the expression of IL-8 and CXCR1 mRNA. However, VEGF down regulate the expression of CXCR2 mRNA during culture period. Expression of IL-1ss and IL-1R1 mRNA was induced in the cultured theca cells at 48h. Our data demonstrates that VEGF stimulated the expression of the IL-8, and CXCR1 genes and that CXCR2 expression was suppressed by VEGF, suggesting a follicle stage-dependent expression pattern for IL-8 system. Furthermore, our results suggest that the transcription system for CXCR genes may have different pathways by VEGF stimulation in bovine theca cells. Taken together, our data suggested that VEGF is associated with the IL system in the theca cells in bovine ovary.
Arici et al. (1996) found that hCG and LH induced higher levels of IL-8 mRNA expression and protein production in human follicles. They also found that progesterone suppressed both basal and IL-1 alpha-stimulated IL-8 expression in stromal and granulosa-lutein cell types.
Ujioka et al. (1998) studied the regulation and involvement of interleukin (IL)-1 beta, IL-8, and IL-1 receptor antagonist in the hCG-induced rabbit ovulatory process. Administration of anti-IL-1 beta antiserum resulted in a statistically significant reduction of the peak level of IL-8 (and IL-1 receptor antagonist). Administration of anti-IL-8 antiserum reduced the accumulation of IL-1 beta and IL-1 receptor antagonist. Anti-IL-1 receptor antagonist antiserum significantly augmented the accumulation of IL-8 (and of IL-1 beta). Runesson E, et al 20001 reported that gonadotropin and cytokine regulate expression of the
chemokine Interleukin 8 in the human preovulatory follicle of
the menstrual cycle.
Follicular-phase ovarian follicular fluid and plasma cytokine profiling ofnatural cycle invitro fertilization patients. Baskind NE 2014 et al.
OBJECTIVE
To characterize follicular fluid (FF) and systemic cytokine profiles at various time points during the natural-cycle follicular and periovulatory phases.
DESIGN
Observational clinical study across two consecutive cycles.
SETTING
Hospital-basedin vitro fertilization program.
PATIENT(S)
Ten women undergoing modified natural-cycle invitro fertilization (MNC-IVF).
INTERVENTION(S)
Plasma and follicular fluid (FF) collection.
MAIN OUTCOME MEASURE(S)
Forty FF cytokine concentrations from individual follicles and plasma from each patient were determined by fluid-phase multiplex immunoassay in two consecutive cycles: 1) tracking cycle-midfollicular or luteal surge; and 2) treatment cycle-periovulatory (at the time of MNC-IVF). Demographic, cycle, and cytokine data were compared with the use of chi-square, paired-scores t test, or Wilcoxon signed ranks tests.
RESULT(S)
Fluctuations in various FF cytokines were evident during the follicular phase: Levels of interleukin (IL) 6 and IL-8 were higher in periovulatory samples, and IL-1 receptor antagonist and vascular endothelial growth factor were elevated earlier in the cycle. Luteal surge profiles were similar to those found in periovulatory samples. Conversely, circulatory cytokine concentrations were more stable during the follicular phase.
CONCLUSION(S)
These findings present an extensive physiologic reference profile of FF cytokines associated with antral folliculogenesis and highlight the compartmentalization of systemic and intraovarian cytokine networks in natural cycles.
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Signal mechanisms of vascular endothelial growth factor and interleukin-8 in ovarian hyperstimulation syndrome: dopamine targets their common pathways. Chen SU et al. BACKGROUND Ovarian hyperstimulation syndrome (OHSS) is a serious complication of ovarian stimulation with massive ascites, pleural effusion and hemoconcentration. The pathophysiological signal mechanisms of OHSS are still unclear and merit further investigation. METHODS Various angiogenic cytokines of follicular fluid and ascites of patients with risk of OHSS were measured, and examined for inducing endothelial permeability. These include vascular endothelial growth factor (VEGF), interleukin (IL)-6, IL-8, basic fibroblast growth factor, tumor necrosis factor-alpha, IL-1alpha, IL-1beta and platelet-derived growth factor. We explore the molecular signal pathways of major contributing cytokines in granulosa-lutein cells and endothelial cells possibly involved in OHSS. RESULTS Neutralizing antibodies of VEGF or IL-8 significantly decreased follicular fluid- and ascites-induced endothelial permeability. Human chorionic gonadotrophin induced VEGF secretion of granulosa-lutein cells through the Sp1 and CREB dependent pathways. IL-8 activated CXCR1/2 of endothelial cells leading to VEGF receptor (VEGFR)-2 transactivation. Both VEGF and IL-8 of follicular fluid enhanced endothelial permeability via VEGFR-2-mediated Rho/Rock activation, actin polymerization and phosphorylations of VE-cadherin and occludin, resulting in opening of adherens junctions and tight junctions. Dopamine (2 microM) inhibited follicular fluid-induced VEGFR-2 signals and endothelial permeability, without diminishing migration and tube formation. CONCLUSIONS Our results suggest that VEGF and IL-8 secreted from corpora luteae may play major roles in OHSS. Delineation of signal pathways would be helpful for treatment. Dopamine may block VEGF- and IL-8-induced endothelial permeability by inhibiting common VEGFR-2 dependent signals.
Chang et al. (1998), detected immunoreactive interleukin-8 in the theca and granulosa cells of human antral follicles. Interleukin-8 messenger ribonucleic acid was demonstrated in theca and granulosa cells of some but not all follicles examined.
Arici et al. (1996) found that granulosa-lutein and ovarian stromal cells express the mRNA and produce the protein.
Neilson et al., (2000) used consecutive application of PCR and serial analysis of gene expression (SAGE) to generate a catalog of approximately 50,000 SAGEtags from nine human oocytes. Matches for known genes were identified using the National Institutes of Health SAGEtag database. IL-8 was found twice in the database.
Lysophosphatidic acid up-regulates expression of interleukin-8 and -6 in granulosa-lutein cells through its receptors and NF-{kappa}B-dependent pathways: implications for angiogenesis of corpus luteum and ovarian hyperstimulation syndrome. Chen SU et al. Context: Lysophosphatidic acid (LPA) was found at significant amounts in follicular fluid of preovulatory follicle. The lysophospholipase D activity of serum from women receiving ovarian stimulation was higher than women with natural cycles. Angiogenic cytokines including interleukin (IL)-6, IL-8 and vascular endothelial growth factor (VEGF) increased in plasma and ascites of patients with ovarian hyperstimulation syndrome (OHSS). The role of LPA in ovarian follicles is unclear. Objective: To investigate the expression of LPA receptors and function of LPA in granulosa-lutein cells. Design: Granulosa-lutein cells were obtained from women undergoing IVF. We examined the expression of LPA receptors using RT-PCR. The effects of LPA on the expression of IL-6, IL-8 and VEGF were examined. Signal pathways of LPA were delineated. The functions of secretory angiogenic factors were tested using human umbilical vein endothelial cells (HUVEC). Results: The LPA1, LPA2 and LPA3 receptors' mRNA was identified in granulosa-lutein cells. LPA enhanced IL-8 and IL-6 expressions in a dose- and time-dependent manner. LPA functioned via LPA receptors, Gi protein, MAPK/ERK, p38, PI3K/Akt and NF-kappaB, and transactivation of epidermal growth factor receptor. LPA induced IL-8 and IL-6 through different pathways. LPA-induced IL-8 and IL-6 increased permeability of HUVEC monolayer. Conclusions: LPA induces IL-8 and IL-6 expressions through LPA receptors and NF-kappaB dependent pathways in granulosa-lutein cells. The LPA in preovulatory follicles may play a role in the angiogenesis of corpus luteum. Large amounts of LPA-induced IL-8 and IL-6 from multiple corpora luteae of stimulated ovaries may be one of the pathophysiological causes of OHSS.
The human ovarian follicular fluid level of interleukin-8 is associated with follicular size and patient age. Malizia BA et al. OBJECTIVE: To investigate the relationship between interleukin-8 (IL-8) in the human ovarian follicle and follicular size, patient age, and fertility factors in IVF cycles. DESIGN: Prospective study. SETTING: University hospital research laboratory and infertility clinic. PATIENT(S): Women undergoing IVF with oocyte retrieval. INTERVENTION(S): Follicular fluid (FF) aspiration, oocyte isolation, FF storage, and experimental studies. MAIN OUTCOME MEASURE(S): Quantization of IL-8 by ELISAs and protein microarray; high-performance liquid chromatography (HPLC) followed by ELISA and Western blotting to evaluate alpha(2)-macroglobulin (alpha(2)M) bound IL-8; association of IL -8 to follicular size, patient age, and IVF outcomes. RESULT(S): Samples of FF from 63 patients contained an average of 629.59 pg/mL of IL-8 with 50%-70% bound to alpha(2)M. Large follicles contained higher levels of IL-8 than small follicles (937.34 vs. 86.97 pg/mL). The IL-8 concentration in the large follicles of women of young age was higher than that of older reproductive age women (1,373.61 vs. 673.29 pg/mL). There were no statistically significant associations found between IL-8 concentration and other IVF cycle factors or pregnancy outcome. CONCLUSION(S): Our findings indicate that IL-8 is present in FF, both in its free and alpha(2)M-bound state, and its concentration is correlated with follicular size and patient age.
Follicle stages
Antral, Preovulatory, Corpus luteum
Comment
Induction of chemokines and prostaglandin synthesis pathways in luteinized human granulosa cells: potential role of luteotropin withdrawal and prostaglandin F2α in regression of the human corpus luteum. Luo W et al. (2015) Our objective was to determine the effects of prostaglandin F2α (PGF2α) and withdrawal of luteotropic stimulants (forskolin or hCG) on expression of chemokines and prostaglandin-endoperoxide synthase 2 (PTGS2) in luteinized human granulosa cells. Human granulosa cells were collected from 12 women undergoing oocyte retrieval and were luteinized in vitro with forskolin or hCG. In first experiment, granulosa-lutein cells were treated with PGF2α, the primary luteolytic hormone in most species. In second experiment, granulosa cells that had been luteinized for 8 d had luteotropins withdrawn for 1, 2, or 3 d. Treatment with PGF2α induced mRNA for chemokine (c-x-c motif) ligand 2 (CXCL2) and CXC ligand 8 (CXCL8; also known as interleukin-8) in granulosa cells luteinized for 8 d but not in cells that were only luteinized for 2 d. Similarly, luteinization of human granulosa cells for 8 d with forskolin or hCG followed by withdrawal of luteotropic stimulants, not only decreased P4 production, but also increased mRNA concentrations for CXCL8, CXCL-2 (after forskolin withdrawal), and PTGS2. These results provide evidence for two key steps in differentiation of luteolytic capability in human granulosa cells. During 8 d of luteinization, granulosa cells acquire the ability to respond to luteolytic factors, such as PGF2α, with induction of genes involved in immune function and PG synthesis. Finally, a decline in luteotropic stimuli triggers similar pathways leading to induction of PTGS2 and possibly intraluteal PGF2α production, chemokine expression, leukocyte infiltration and activation, and ultimately luteal regression.//////////////////
In studying the neutrophil-interleukin-8 system in human folliculogenesis, Chang et al. (1998) concluded that neutrophils are present in the theca of developing antral follicles, increase in
Runesson et al. (1996) identified the human preovulatory follicle as a source of the chemotactic cytokine interleukin-8.