Molecular Human Reproduction, Vol. 7, No. 8, 741-746,
August 2001
© 2001 European Society of Human Reproduction and Embryology
Uterine physiology |
Expression and regulation of growth-regulated oncogene 
in human endometrial stromal cells
Department of Obstetrics and Gynecology, Oita Medical University, Hasama-machi, Oita 879-5593, Japan
Abstract
Growth-regulated oncogene 
(GRO), a potent chemoattractant for neutrophils, has previously been detected in the endometrial stromal cells (ESC) of human endometrium. In this study, the mRNA expression of GRO in the endometrium was evaluated by reverse transcription–polymerase chain reaction analysis, while the localization of GRO protein was studied by immunohistochemistry and the concentrations of GRO were measured using an enzyme-linked immunosorbent assay (ELISA). The effects of known modulators of endometrial function on the production of GRO by ESC were also examined by ELISA and Northern blot analysis. The expression of both GRO mRNA and GRO protein was detected in the cycling endometrium. GRO protein was localized mainly in the stroma, and endometrial tissues in the secretory phase contained higher amounts of GRO protein than did those in the proliferative phase. The production of GRO by ESC was enhanced by in-vitro decidualization. Lipopolysaccharide, tumour necrosis factor- and interleukin-1ß also stimulated the expression of GRO mRNA and protein by ESC. These results suggest that the production of GRO by ESC is regulated by ovarian steroid hormones as well as by inflammatory mediators. The modulation of GRO concentrations in the local environment may contribute to normal and pathological processes in the uterus by regulating leukocyte trafficking in the endometrium.
cytokine network/endometrial stromal cell/growth-regulated oncogene /menstrual cycle
Introduction
Chemokines are a large superfamily of structurally and functionally related molecules with chemotactic activity targeted at specific leukocyte populations. They are 70–90 amino acids in length and are divided into four subfamilies based on the relative position of their cysteine residues (CC, CXC, C, CXC3) (Schall, 1991
; Miller and Krangel, 1992; Baggiolini et al., 1994; Kelner et al., 1994; Luster, 1998). The CC chemokine subfamily includes macrophage inflammatory protein (MIP)-1, MIP-1ß, macrophage chemoattractant protein-1 (MCP-1), regulated upon activation, normal T cell expressed and secreted (RANTES), I-309, and HC14, all of which mainly chemoattract and activate mononuclear cells (Oppenheim et al., 1991; Schall, 1991; Baggiolini et al., 1994). In contrast, the CXC chemokine subfamily includes interleukin (IL)-8, neutrophil-activating protein-2, platelet factor 4, ß-thromboglobulin, growth-regulated oncogenes (GRO) , GROß and GRO
, and interferon--inducible protein 10, many of which have been shown to chemoattract and activate neutrophils (Miller and Krangel, 1992; Baggiolini et al., 1994; Taub and Oppenheim, 1994).
Human endometrial stromal cells (ESC) have been reported to produce and secrete various chemokines, including interleukin IL-8 (Arici et al., 1993; Nasu et al., 1998a,b,1999a), GRO (Oral et al., 1996), MCP-1 (Nasu et al., 1998a,b,1999a), MIP-1 (Nasu et al., 1999a) and RANTES (Arima et al., 2000). The expression of these cytokines has been suggested to be important in menstruation, bacterial infection, implantation, and in the maintenance of early pregnancy (Chard, 1995; Garcia-Velasco and Arici, 1999).
Of these chemokines, GRO is a 73 amino acid, 8 kDa protein that belongs to the CXC chemokine family and has neutrophil-activating and -chemoattracting properties similar to those of IL-8 (Derynck et al., 1990; Schröder et al., 1990a,b; Moser et al., 1990,1991). GRO was initially discovered as a growth-regulated gene that is overexpressed constitutively in tumorigenic cells and transcribed in normal cells only during growth stimulation (Sager et al., 1992). Independently, a melanoma growth-stimulating activity (MGSA) was cloned from a human melanoma cell line, Hs294T, and found to be identical to human GRO (Richmond et al., 1988). At the present time, in addition to the initially cloned GRO, two additional human GRO proteins, GROß or MIP-2 and GRO or MIP-2ß, which share 90 and 86% amino acid sequence homology, respectively, with GRO, have been identified (Haskill et al., 1990; Moser et al., 1990; Tekamp-Olson et al., 1990). The GRO cDNA encodes a 107 amino acid precursor protein from which the N-terminal 34 amino acid residues are cleaved to generate the 73 amino acid residue mature GRO. GRO exhibits a growth stimulatory activity for the human Hs294T melanoma cell line from which it was initially isolated. As a chemokine member, GRO, like IL-8, is a potent chemoattractant for human neutrophils and stimulates neutrophil degranulation and enzyme release from cytochalasin B-treated human neutrophils (Sager et al., 1992). GRO expression is inducible by serum or platelet-derived growth factor (PDGF) and/or by a variety of inflammatory mediators such as lipopolysaccharide (LPS), IL-1, and tumour necrosis factor (TNF) in monocytes (Schröder et al., 1990
), fibroblasts, synovial cells (Golds et al., 1989), melanocytes, mammary epithelial cells (Jaffe et al., 1993), and endothelial cells (Wen et al., 1989; Sager et al., 1992). In addition, GRO gene expression within inflammatory lesions has been implicated in neutrophil recruitment to inflamed skin (Kojima et al., 1993), lungs (Becker et al., 1994), joints (Koch et al., 1995), and kidneys (Wu et al., 1995). Recently, GRO expression has been detected in the human endometrium and is suggested to be involved in the pathogenesis of endometriosis (Oral et al., 1996).
In this study, we investigated the expression of GRO in endometrial tissue and the effects of known modulators of endometrial function on the expression of the GRO transcript and protein by cultured ESC which have been shown to produce various CC and CXC chemokines. In addition, we discuss the regulation of GRO expression in the cytokine network in the cyclic endometrium.
Materials and methods
Tissue preparation for protein and RNA isolation
Normal endometrial specimens were obtained from 15 premenopausal patients who had undergone hysterectomies for intramural leiomyomas. Seven specimens were diagnosed as proliferative phase (4th to 14th day of the menstrual cycle) and eight as secretory phase (16th to 27th day of the menstrual cycle) on the basis of standard histological criteria. Each tissue sample (100 mg) was soaked in 1 ml of TRIzol reagent (Gibco-BRL, Gaithersburg, MD, USA) and homogenized through the use of a Polytron (Type PT 10/35; Kinmatica GmbH, Luzern, Switzerland). The tissue proteins and RNA were isolated according to the manufacturer's instructions (Trizol; Gibco-BRL). The RNA precipitate was dissolved in DEPC-treated water. The protein precipitate was dissolved in 0.3 ml of phosphate-buffered saline (PBS) containing 10 mmol/l PMSF (Sigma, St Louis, MO, USA) and 1 mmol/l leupeptin (Sigma), and the amounts of protein were measured using a Coomassie protein assay reagent kit (Pierce, Rockford, IL, USA), while the amounts of GRO were measured using a commercially available enzyme-linked immunosorbent assay (ELISA) kit (R&D systems, Minneapolis, MN, USA). The sensitivity of the assay for GRO was 5 pg/ml.
Detection of GRO mRNA in endometrium by RT–PCR
To evaluate the expression of GRO mRNA in normal endometrium, we amplified the GRO transcript by the reverse transcriptase–polymerase chain reaction (RT–PCR) method using an RNA PCR kit with AMV RTase (Takara, Tokyo, Japan) as previously described (Nasu et al., 1999b). The total RNA isolated from 15 samples of normal endometrial tissues was reverse-transcribed into complementary DNA (cDNA). To perform the PCR, primer sets for GRO (sense primer: 5'-GAACTGCGCTGCCAGTG-3' and antisense primer: 5'-GGCATGTTGCAGGCTCCTCA-3') (Haskill et al., 1990) were synthesized by the phosphoramide method on a DNA synthesizer (Model 8700; Biosearch, San Rafael, CA, USA) and purified on Sephadex G50 columns (Pharmacia LKB Biotechnology) and by high performance liquid chromatography. The predicted size of the PCR product was 580 bp. The cDNA transcribed from 1 µg of total RNA was amplified using a thermal cycler (Model PJ2000; Perkin Elmer, Norwalk, CT, USA). The PCR with primer pairs for GRO was performed for 35 cycles, with each cycle consisting of denaturation at 94°C for 1 min, annealing at 65°C for 1 min, and an extension at 72°C for 1 min. The PCR products were separated by 1.5% agarose gel (Takara) electrophoresis and visualized by ethidium bromide (Takara) staining. The PCR product was cloned with a TA cloning kit (Invitrogen, Leek, Netherlands) and used as a probe in the Northern blot analysis. Sequence analysis of the PCR products was also performed to confirm that the amplified cDNA were GRO transcripts.
Detection of GRO protein in endometrium by double indirect immunohistochemistry
Seven endometrial specimens in the proliferative phase and eight in the secretory phase were processed for double indirect immunohistochemistry as previously described (Nasu et al., 2000). Briefly, tissues were fixed in 3% paraformaldehyde for 30 min, washed three times in PBS, infiltrated with 5–15% sucrose followed by Tissue-TekTM OCT compound (OCT) (Miles Scientific, Naperville, IL, USA), and frozen in liquid nitrogen. Sections (6 µm) were prepared using a cryostat (Slee International Inc., Tiverton, RI, USA) and collected on poly-L-lysine-coated microscope slides (Dako, Copenhagen, Denmark). Fixed sections were permeabilized in cold methanol for 5 min, washed three times in PBS for 5 min, and incubated for 30 min with 1% bovine serum albumin (Sigma) in PBS. Sections were then incubated for 1 h with two primary antibodies [mouse anti-GRO monoclonal antibody (R&D systems) and rabbit anti-cytokeratin polyclonal antibody (Dako)], followed by rinsing three times in PBS for 5 min. The sections were then incubated with secondary antibodies conjugated to fluorescein or rhodamine (fluorescein-labelled donkey anti-mouse IgG and rhodamine-labelled donkey anti-rabbit IgG, Jackson Immunoresearch Laboratories, West Grove, PA, USA), washed three times in PBS for 5 min, and mounted with Vectorshield (Vector Laboratories, Burlingame, CA, USA). All incubations and washes were performed at room temperature. Samples were viewed with a Zeiss Axiophot Epifluorescence microscope (Carl Zeiss, Oberkochen, Germany) equipped with filters to selectively view the fluorescein and rhodamine fluorescence.
ESC isolation procedure
For the isolation and culture of ESC, seven endometrial specimens in the late proliferative phase were utilized. Normal ESC were separated from the epithelial glands by digesting the tissue fragments with collagenase as previously described (Arici et al., 1993; Nasu et al., 1998a,b). After three passages (15–20 days after isolation) by standard methods of trypsinization, the cells were >98% pure as analysed by immunocytochemical staining with antibodies to vimentin (V9, Dako), keratin (Dako), factor VIII (Dako), and leukocyte common antigen (2B11+PD7/26, Dako) and, as such, were ready to be used for the experiments.
Detection of GRO in the culture media of ESC by ELISA
To study the production of GRO by ESC, 1x106 cells were plated on 6-well culture plates (Corning, New York, NY, USA) in 1 ml of Roswell Park Memorial Hospital 1640 medium (Gibco-BRL) supplemented with 10% heat-inactivated fetal bovine serum (FBS; Gibco-BRL) and cultured until they were fully confluent. The medium was replaced with fresh culture medium containing various amounts of 12-O-tetradecanoylphorbol 13-acetate (TPA, 0.001–100 nmol/l; Sigma), LPS (0.001–1 µg/ml; Sigma), recombinant human IL-1ß (0.001–10 ng/ml; R&D systems), recombinant human TNF- (0.01–100 ng/ml; R&D systems), recombinant human interferon- (IFN-, 0.01–100 U/ml; R&D systems), or human PDGF (0.001–10 ng/ml; R&D systems). The effects of ethinyl oestradiol-17ß (10 nmol/l; Sigma), medroxyprogesterone acetate (MPA, 100 nmol/l; Sigma), and the combination of these two steroid hormones on GRO production were also examined. Under these conditions, the medium was collected 24 h after stimulation and stored at –70°C until assayed. To evaluate the effects of FBS on GRO production, the medium from cells cultured without FBS was also examined.
Decidualization of cultured ESC was induced by incubating the cells with 0.5 mmol/l of didutyryl-cAMP (db-cAMP, Sigma) and 100 nmol/l of MPA as previously described (Tang et al., 1993). The culture medium was replaced every 3 days. After 12 days of treatment under these conditions, the medium was replaced with fresh culture medium containing the same amounts of db-cAMP and MPA, and the cells were further cultured for 24 h. The medium was collected and stored at –70°C until assayed.
The isolated cells from each patient were used for one experiment at a time, and each experiment, performed in triplicate, was repeated four times. The concentrations of GRO were determined in the supernatants with a commercially available ELISA (R&D systems). The concentrations of prolactin were also determined in the supernatant of decidualized ESC with a microparticle enzyme immunoassay (Abbott Laboratories, North Chicago, IL, USA) and were used as a marker for decidualization. The sensitivity of the assay for prolactin was 0.1 ng/ml.
Northern blot analysis for GRO mRNA expression in ESC
To study the expression of GRO mRNA in ESC, 5x106 cells were plated on 75 cm2 culture flasks (Corning) in 15 ml of culture medium with 10% heat-inactivated FBS and were cultured until fully confluent. The medium was replaced with fresh culture medium containing various amounts of LPS (0.001–1 µg/ml), recombinant human IL-1ß (0.001–100 ng/ml), or recombinant human TNF- (0.01–100 ng/ml), and the cells were further cultured for 0–24 h. The decidualization of cultured ESC was induced by db-cAMP and MPA as described above. mRNA extraction and Northern blotting was performed as previously described (Nasu et al., 1999a,b).
Statistical analysis
Data are presented as mean ± SD and were appropriately analysed by the Student's t-test and the Bonferroni/Dunn test with StatView 4.5 (Abacus Concepts, Berkeley, CA, USA). P < 0.05 was accepted as statistically significant.
Results
Detection of GRO mRNA and protein in the endometrial tissue
GRO protein was detected in all protein extracts from the endometrial tissues. As shown in Figure 1, GRO protein concentrations in secretory-phase endometrium were significantly higher than those in proliferative-phase endometrium. Using fluorescence immunocytochemistry, GRO protein was localized focally in the stroma of endometrium in all specimens (Figure 2)
.
|
|
GRO
mRNA was detected by RT–PCR in all specimens of proliferative-phase and secretory-phase endometrium (data not shown). The results of the sequence analysis of cDNA fragments amplified by RT–PCR were consistent with the previously reported sequence of human GRO (Anisowicz et al., 1987; Haskill et al., 1990). We used this cDNA fragment as a probe for GRO in the Northern blot analysis.
Detection of GRO in the culture media of ESC
The concentration of GRO in the culture medium without cells was below the level of detection. As shown in Figure 3A, low concentrations of GRO protein were detected in the culture medium of non-stimulated ESC from proliferative endometrium incubated for 24 h. Serum starvation had an inhibitory effect on the production of GRO by ESC. For the following experiments, therefore, we used the cells isolated from proliferative endometrium and cultured with media containing heat-inactivated 10% FBS.
|
As shown in Figure 3B
, the concentrations of GRO were increased with increasing concentrations of LPS. LPS showed the strongest effects at concentrations of 0.01 µg/ml. The concentrations of GRO were also increased with increasing concentrations of IL-1ß (Figure 3C). TNF- also increased the GRO secretion by ESC in a dose-dependent manner (Figure 3D), whereas TPA, IFN-, PDGF, ethinyl oestradiol, MPA, and the combination of these two steroid hormones, ethinyl oestradiol + MPA, did not affect GRO secretion by ESC (data not shown).
Prolactin, a marker for the decidualization of ESC, was not detected in the supernatant of non-decidualized ESC (<0.1 ng/ml); however, prolactin production was induced in decidualized ESC (36.3 ± 1.9 ng/ml). In-vitro decidualization greatly enhanced the production of GRO by cultured ESC (Figure 3E).
mRNA expression for GRO in ESC
The expression of mRNA for GRO was below detectable levels in non-stimulated ESC. GRO mRNA expression was induced by IL-1ß, TNF-, and LPS in a dose-dependent manner (Figure 4A–C
)
. The expression of GRO mRNA after stimulation with these agents was quickly induced to its highest levels within 4 h and maintained at plateau levels up to 12 h (data not shown). Decidualization also enhanced the expression of GRO mRNA in cultured ESC (Figure 4D).
|
Discussion
Chemokines are key components in the process of leukocyte recruitment from vasculature into tissues. The interaction of different chemokines with their receptors on leukocytes allows for the selective activation and chemotaxis of neutrophils, eosinophils, lymphocytes, or monocytes necessary for migration to the sites of evolving inflammation. We have previously reported the production of chemokines, IL-8 (Nasu et al., 1998a,b,1999a), MCP-1 (Nasu et al., 1998a,b,1999a), MIP-1 (Nasu et al., 1999a) and RANTES (Arima et al., 2000) by human ESC and have suggested a paracrine regulation of these chemokines in cyclic endometrium and during early pregnancy.
In the present study, we demonstrated that GRO mRNA and protein are expressed in normal cyclic endometrium and that the concentrations of GRO protein are higher in the secretory phase than proliferative phase. GRO protein was localized focally in the stroma of the endometrium. In-vitro decidualization enhanced the expression of GRO by ESC. These results suggest that GRO is produced constitutively in the endometrial stroma and may be regulated, at least in part, by ovarian steroid hormones through the induction of differentiation of ESC. The expression of IL-8, another member of the CXC chemokine family, is also regulated by progesterone (Arici et al., 1996). It has been suggested that the ovarian steroid hormone-regulated expression of CXC chemokines might be important in the physiological changes of the normal cyclic endometrium.
Because GRO and IL-8 are similar in many respects, we examined the effects of known modulators of endometrial function on GRO production by ESC. In this study, we demonstrated that LPS, IL-1ß and TNF-, which have been shown to induce IL-8 production by ESC, also enhance GRO production by these cells, as previously reported (Oral et al., 1996). Enhanced expression of GRO by proinflammatory cytokines and LPS may be involved in pathological conditions, such as bacterial infection. In addition, since small amounts of IL-1ß and TNF- have been detected in the normal endometrium, these proinflammatory cytokines may also be implicated in the physiological control of GRO production by ESC. It is interesting that TPA, a stimulator of IL-8 expression by ESC (Nasu et al., 1998a), and IFN-, an inhibitor of IL-8 expression by ESC (Nasu et al., 1998b), did not affect GRO production by these cells. These results suggest that GRO and IL-8 might be differently regulated, at least in part, in the endometrial cytokine network.
In summary, we have demonstrated that GRO is expressed in ESC of the cycling endometrium and that the differentiation of ESC, i.e. decidualization, is implicated in GRO expression. LPS, TNF-, and IL-1ß also stimulate the GRO production by cultured human ESC. However, TPA and IFN- do not appear to affect the production of this chemokine, suggesting that the regulatory mechanism of GRO is different, at least in part, from that of IL-8. The modulation of GRO concentrations in the local environment may contribute to the normal and pathological processes associated with reproduction by regulating leukocyte trafficking in the endometrium.
Acknowledgements
This research was supported in part by the Ministry of Education, Science, and Culture of Japan Grant-in-Aid 11770945 (to K.N.) and 09671699 (to I.M.) for Scientific Research.
Notes
1 To whom correspondence should be addressed. E-mail: nasu{at}oita-med.ac.jp 
References
Anisowicz, A., Bardwell, L. and Sager, R. (1987) Constitutive overexpression of a growth-regulated gene in transformed Chinese hamster and human cells. Proc. Natl. Acad. Sci. USA, 84, 7188–7192.
Arici, A., Head, J.R., MacDonald, P.C. et al. (1993) Regulation of interleukin-8 gene expression in human endometrial cells in culture. Mol. Cell. Endocrinol., 94, 195–204.[ISI][Medline]
Arici, A., McDonald, P.C. and Casey, M.L. (1996) Progestin regulation of interleukin-8 mRNA levels and protein synthesis in human endometrial stromal cells. J. Steroid Biochem. Mol. Biol., 58, 71–76.[ISI][Medline]
Arima, K., Nasu, K., Narahara, H. et al. (2000) Effects of lipopolysaccharide and cytokines on production of RANTES by cultured human endometrial stromal cells. Mol. Hum. Reprod., 6, 246–251.
Baggiolini, M., Dewald, B. and Moser, B. (1994) Interleukin-8 and related chemotactic cytokines–CXC and CC chemokines. Adv. Immunol., 55, 97–179.[ISI][Medline]
Becker, S., Quay, J., Koren, H.S. et al. (1994) Constitutive and stimulated MCP-1, GRO, ß, and expression in human airway epithelium and bronchoalveolar macrophages. Am. J. Physiol., 266, L278–L286.
Chard, T. (1995) Cytokines in implantation. Hum. Reprod. Update, 1, 385–396.
Derynck, R., Balentien, E., Han, J.H. et al. (1990) Recombinant expression, biochemical characterization, and biological activities of the human MGSA/gro protein. Biochemistry, 29, 10225–10233.[Medline]
Garcia-Velasco, J.A. and Arici, A. (1999) Chemokines and human reproduction. Fertil. Steril., 71, 983–993.[ISI][Medline]
Golds, E.E., Mason, P. and Nyirkos, P. (1989) Inflammatory cytokines induce synthesis and secretion of gro protein and a neutrophil chemotactic factor but not ß2-microglobulin in human synovial cells and fibroblasts. Biochem. J., 259, 585–588.[ISI][Medline]
Haskill, S., Peace, A., Morris, J. et al. (1990) Identification of three related human GRO genes encoding cytokine functions. Proc. Natl. Acad. Sci. USA, 87, 7732–7736.
Jaffe, G.J., Richmond, A., Van Le, L. et al. (1993) Expression of three forms of melanoma growth stimulatory activity (MGSA)/gro in human retinal pigment epithelial cells. Invest. Ophthalmol. Vis. Sci., 34, 2776–2785.
Kelner, G.S., Kennedy, J., Bacon, K.B. et al. (1994) Lymphotactin: a cytokine that represents a new class of chemokine. Science, 266, 1395–1399.
Koch, A.E., Kunkel, S.L., Shah, M.R. et al. (1995) Growth-related gene product . A chemotactic cytokine for neutrophils in rheumatoid arthritis. J. Immunol., 155, 3660–3666.[Abstract]
Kojima, T., Cromie, M.A., Fisher, G.J. et al. (1993) GRO- mRNA is selectively overexpressed in psoriatic epidermis and is reduced by cyclosporin A in vivo, but not in cultured keratinocytes. J. Invest. Dermatol., 101, 767–772.[ISI][Medline]
Luster, A.D. (1998) Chemokines: chemotactic cytokines that mediate inflammation. N. Engl. J. Med., 338, 436–445.
Miller, M.D. and Krangel, M.S. (1992) Biology and biochemistry of the chemokines: a family of chemotactic and inflammatory cytokines. Crit. Rev. Immunol., 12, 17–46.[ISI][Medline]
Moser, B., Clark-Lewis, I., Zwahlen, R. et al. (1990) Neutrophil-activating properties of the melanoma growth-stimulatory activity. J. Exp. Med., 171, 1797–1802.
Moser, B., Schumacher, C., Von Tscharner, V. et al. (1991) Neutrophil-activating peptide 2 and GRO/melanoma growth-stimulatory activity interact with neutrophil-activating peptide 1/interleukin-8 receptors on human neutrophils. J. Biol. Chem., 266, 10666–10671.
Nasu, K., Matsui, N., Narahara, H. et al. (1998a) MaMi, a human endometrial stromal sarcoma cell line that constitutively produces interleukin (IL)-6, IL-8, and monocyte chemoattractant protein-1. Arch. Pathol. Lab. Med., 122, 836–841.[ISI][Medline]
Nasu, K., Matsui, N., Narahara, H. et al. (1998b) Effects of interferon- on cytokine production by endometrial stromal cells. Hum. Reprod., 13, 2598–2601.
Nasu, K., Narahara, H., Matsui, N. et al. (1999a) Platelet-activating factor stimulates cytokine production by human endometrial stromal cells. Mol. Hum. Reprod., 5, 548–553.
Nasu, K., Sugano, T., Matsui, N. et al. (1999b) Expression of hepatocyte growth factor in cultured human endometrial stromal cells is induced through a protein kinase C-dependent pathway. Biol. Reprod., 60, 1183–1187.
Nasu, K., Zhou, Y., McMaster, M.T. and Fisher, S.J. (2000) Upregulation of human cytotrophoblast invasion by hepatocyte growth factor. J. Reprod. Fertil., 55 (Suppl.), 73–80.
Oppenheim, J.J., Zachariae, C.O., Mukaida, N. et al. (1991) Properties of the novel proinflammatory supergene `intercrine' cytokine family. Annu. Rev. Immunol., 9, 617–648.[ISI][Medline]
Oral, E., Seli, E., Bahtiyar, M.O. et al. (1996) Growth-regulated expression in the peritoneal environment with endometriosis. Obstet. Gynecol., 88, 1050–1056.[Abstract]
Richmond, A., Balentien, E., Thomas, H.G. et al. (1988) Molecular characterization and chromosomal mapping of melanoma growth stimulatory activity, a growth factor structurally related to ß-thromboglobulin. EMBO J., 7, 2025–2033.[ISI][Medline]
Sager, R., Anisowicz, A., Pike, M.C. et al. (1992) Structural, regulatory, and functional studies of the GRO gene and protein. Cytokine, 4, 96–116.[ISI][Medline]
Schall, T.J. (1991) Biology of the RANTES/SIS cytokine family. Cytokine, 3, 165–183.[ISI][Medline]
Schröder, J.M., Persoon, N.L. and Christophers, E. (1990a) Lipopolysaccharide-stimulated human monocyte secretes, apart from neutrophil-activating peptide 1/interleukin-8, a second neutrophil-activating protein: NH2-terminal aminoacid sequence identity with melanoma growth stimulatory activity. J. Exp. Med., 171, 1091–1100.
Schröder, J.M., Sticherling, M., Henneicke, H.H. et al. (1990b) IL-1 or TNF-ß stimulate release of three NAP-1/IL-8-related neutrophil chemotactic proteins in human dermal fibroblasts. J. Immunol., 144, 2223–2232.[Abstract]
Tang, B., Guller, S. and Gurpide, E. (1993) Cyclic adenosine 3',5'-monophosphate induces prolactin expression in stromal cells isolated from human proliferative endometrium. Endocrinology, 133, 2197–2203.[Abstract]
Taub, D.D. and Oppenheim, J.J. (1994) Chemokines, inflammation and the immune system. Ther. Immunol., 1, 229–246.[Medline]
Tekamp-Olson, P., Gallegos, C., Bauer, D. et al. (1990) Cloning and characterization of cDNAs for murine macrophage inflammatory protein 2 and its human homologues. J. Exp. Med., 172, 911–919.
Wen, D., Rowland, A. and Derynck, R. (1989) Expression and secretion of gro/MGSA by stimulated human endothelial cells. EMBO J., 8, 1761–1766.[ISI][Medline]
Wu, X., Dolecki, G.J. and Lefkowith, J.B. (1995) GRO chemokines: a transduction, integration, and amplification mechanism in acute renal inflammation. Am. J..Physiol., 269, F248–F256.
Submitted on April 2, 2001; accepted on June 13, 2001.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  C.-w. Cheng, H. Bielby, D. Licence, S. K. Smith, C. G. Print, and D. S. Charnock-Jones Quantitative Cellular and Molecular Analysis of the Effect of Progesterone Withdrawal in a Murine Model of Decidualization Biol Reprod, May 1, 2007; 76(5): 871 - 883. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A.P. Hess, A.E. Hamilton, S. Talbi, C. Dosiou, M. Nyegaard, N. Nayak, O. Genbecev-Krtolica, P. Mavrogianis, K. Ferrer, J. Kruessel, et al. Decidual Stromal Cell Response to Paracrine Signals from the Trophoblast: Amplification of Immune and Angiogenic Modulators Biol Reprod, January 1, 2007; 76(1): 102 - 117. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Rossi, A. M Sharkey, P. Vigano, G. Fiore, R. Furlong, P. Florio, G. Ambrosini, S. K Smith, and F. Petraglia Identification of genes regulated by interleukin-1{beta} in human endometrial stromal cells Reproduction, November 1, 2005; 130(5): 721 - 729. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Nishida, K. Nasu, J. Fukuda, Y. Kawano, H. Narahara, and I. Miyakawa Down-Regulation of Interleukin-1 Receptor Type 1 Expression Causes the Dysregulated Expression of CXC Chemokines in Endometriotic Stromal Cells: A Possible Mechanism for the Altered Immunological Functions in Endometriosis J. Clin. Endocrinol. Metab., October 1, 2004; 89(10): 5094 - 5100. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Kitaya, T. Nakayama, N. Daikoku, S. Fushiki, and H. Honjo Spatial and Temporal Expression of Ligands for CXCR3 and CXCR4 in Human Endometrium J. Clin. Endocrinol. Metab., May 1, 2004; 89(5): 2470 - 2476. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Kitaya, T. Nakayama, T. Okubo, H. Kuroboshi, S. Fushiki, and H. Honjo Expression of Macrophage Inflammatory Protein-1{beta} in Human Endometrium: Its Role in Endometrial Recruitment of Natural Killer Cells J. Clin. Endocrinol. Metab., April 1, 2003; 88(4): 1809 - 1814. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Sun, K. Nasu, J. Fukuda, S. Mine, M. Nishida, and I. Miyakawa Expression of macrophage inflammatory protein-3{alpha} in an endometrial epithelial cell line, HHUA, and cultured human endometrial stromal cells Mol. Hum. Reprod., October 1, 2002; 8(10): 930 - 933. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Kai, K. Nasu, S. Nakamura, J. Fukuda, M. Nishida, and I. Miyakawa Expression of interferon-{gamma}-inducible protein-10 in human endometrial stromal cells Mol. Hum. Reprod., February 1, 2002; 8(2): 176 - 180. [Abstract] [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||