Monocyte chemotactic protein-1, a member of the small inducible gene (SIG) family, plays a role in the recruitment of monocytes to sites of injury and infection. Yoshimura et al. (1989) isolated a full-length cDNA clone of the MCP1 gene. MCP1 mRNA was induced in human peripheral blood mononuclear leukocytes by phytohemagglutinin (PHA), lipopolysaccharide, and IL1, but not by IL2, TNF, or IFN-gamma.
Elevated C-reactive protein and monocyte chemoattractant protein-1 in patients with polycystic ovary syndrome. Hu W et al. OBJECTIVES: C-reactive protein (CRP) and monocyte chemoattractant protein-1 (MCP-1) are inflammatory factors involved in the pathogenesis of atherosclerosis. This study aimed to analyse serum concentrations of CRP and MCP-1 in patients with polycystic ovary syndrome (PCOS), and to test the effect of these factors on human THP-1 cells to determine the inflammatory state of these patients. STUDY DESIGN: Eighty-five women with PCOS and 65 healthy women with regular menstrual cycles, matched for age and body mass index (BMI), were included in the study. Serum total cholesterol, triglycerides, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein-cholesterol, fasting glucose and fasting insulin were monitored. Serum CRP and MCP-1 were compared between patients with PCOS and controls. Phorbol 12-myristate 13-acetate was used to induce the differentiation of human THP-1 monocytes into THP-1 macrophages. THP-1 macrophages were incubated with serum from patients with PCOS or controls for 24h, and MCP-1 mRNA expression was determined using real-time reverse transcriptase polymerase chain reaction. RESULTS: Serum CRP and MCP-1 levels were significantly higher in women with PCOS compared with controls (CRP 1.9?2.0mg/l vs. 0.9?0.8mg/l; MCP-1 125.7?68.0ng/ml vs. 89.8?68.3ng/ml, respectively). Serum CRP level was positively correlated with BMI (r=0.494, p=0.000), waist:hip ratio (r=0.451, p=0.000), testosterone (r=0.214, p=0.032), homeostasis model assessment of insulin resistance (HOMA-IR; r=0.617, p=0.000) and MCP-1 (r=0.219, p=0.027), and negatively correlated with HDL-C (r=-0.209, p=0.035). MCP-1 level was positively correlated with BMI (r=0.381, p=0.000), waist:hip ratio (r=0.421, p=0.000), HOMA-IR (r=0.265, p=0.007) and triglycerides (r=0.439, p=0.000). MCP-1 mRNA expression in THP-1 cells incubated with serum from patients with PCOS was significantly higher than that in THP-1 cells incubated with serum from controls (p<0.05). CONCLUSION: Patients with PCOS suffer low-grade chronic inflammation indicated by higher levels of CRP and MCP-1, which could lead to increased risk of atherogenesis.
NCBI Summary:
This gene is one of several cytokine genes clustered on the q-arm of chromosome 17. Chemokines are a superfamily of secreted proteins involved in immunoregulatory and inflammatory processes. The superfamily is divided into four subfamilies based on the arrangement of N-terminal cysteine residues of the mature peptide. This chemokine is a member of the CC subfamily which is characterized by two adjacent cysteine residues. This cytokine displays chemotactic activity for monocytes and basophils but not for neutrophils or eosinophils. It has been implicated in the pathogenesis of diseases characterized by monocytic infiltrates, like psoriasis, rheumatoid arthritis and atherosclerosis. It binds to chemokine receptors CCR2 and CCR4. [provided by RefSeq, Jul 2013]
General function
Ligand, Cytokine
Comment
Cellular localization
Comment
Serum and follicular fluid monocyte chemotactic protein-1 levels are elevated in obese women and are associated with poorer clinical pregnancy rate after in vitro fertilization: a pilot study. Buyuk E et al. (2017) To determine whether monocyte chemotactic protein-1 (MCP-1), a proinflammatory chemokine important in ovulation, is abnormally elevated in obese women undergoing IVF and whether serum and follicular fluid (FF) levels of MCP-1 are associated with IVF outcome. Prospective pilot study. Academic center. Women undergoing IVF. Serum and FF were collected from women undergoing IVF. Correlation between MCP-1 and other inflammatory markers with adiposity and pregnancy outcome after IVF. Obese women had significantly higher serum and FF MCP-1 levels compared with overweight and normal weight women. Serum MCP-1, granulocyte colony stimulating factor, catalase, and C-reactive protein (CRP) were positively correlated with body mass index (BMI). After adjusting for age and baseline FSH, these correlations remained significant for serum MCP-1, granulocyte colony stimulating factor, and CRP. In the FF, only MCP-1 was positively correlated with BMI. Women who became pregnant had significantly lower serum MCP-1 and CRP levels compared with those who did not become pregnant; this difference was more pronounced among women with diminished ovarian reserve. Receiver operating characteristic curve demonstrated that serum MCP-1 levels >373.0 pg/mL in all women and >362.6pg/mL in women with diminished ovarian reserve predicted failure to achieve a clinical pregnancy. Elevations in serum and FF MCP-1 levels are positively correlated with adiposity and negatively correlated with pregnancy rates (PRs) in women undergoing IVF.//////////////////
Elevated C-reactive protein and monocyte chemoattractant protein-1 in patients with polycystic ovary syndrome. Hu W et al. (2011) C-reactive protein (CRP) and monocyte chemoattractant protein-1 (MCP-1) are inflammatory factors involved in the pathogenesis of atherosclerosis. This study aimed to analyse serum concentrations of CRP and MCP-1 in patients with polycystic ovary syndrome (PCOS), and to test the effect of these factors on human THP-1 cells to determine the inflammatory state of these patients. Eighty-five women with PCOS and 65 healthy women with regular menstrual cycles, matched for age and body mass index (BMI), were included in the study. Serum total cholesterol, triglycerides, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein-cholesterol, fasting glucose and fasting insulin were monitored. Serum CRP and MCP-1 were compared between patients with PCOS and controls. Phorbol 12-myristate 13-acetate was used to induce the differentiation of human THP-1 monocytes into THP-1 macrophages. THP-1 macrophages were incubated with serum from patients with PCOS or controls for 24h, and MCP-1 mRNA expression was determined using real-time reverse transcriptase polymerase chain reaction. Serum CRP and MCP-1 levels were significantly higher in women with PCOS compared with controls (CRP 1.9±2.0 mg/l vs. 0.9±0.8 mg/l; MCP-1 125.7±68.0 ng/ml vs. 89.8±68.3 ng/ml, respectively). Serum CRP level was positively correlated with BMI (r=0.494, p=0.000), waist:hip ratio (r=0.451, p=0.000), testosterone (r=0.214, p=0.032), homeostasis model assessment of insulin resistance (HOMA-IR; r=0.617, p=0.000) and MCP-1 (r=0.219, p=0.027), and negatively correlated with HDL-C (r=-0.209, p=0.035). MCP-1 level was positively correlated with BMI (r=0.381, p=0.000), waist:hip ratio (r=0.421, p=0.000), HOMA-IR (r=0.265, p=0.007) and triglycerides (r=0.439, p=0.000). MCP-1 mRNA expression in THP-1 cells incubated with serum from patients with PCOS was significantly higher than that in THP-1 cells incubated with serum from controls (p<0.05). Patients with PCOS suffer low-grade chronic inflammation indicated by higher levels of CRP and MCP-1, which could lead to increased risk of atherogenesis.//////////////////
Direct role of the C-C motif chemokine receptor 2/monocyte chemoattractant protein 1 system in the feline cumulus oocyte complex. Rojo JL et al. (2018) Studies were designed to a) evaluate the mRNA expression of the C-C motif chemokine receptor 2 (CCR2) and its chemokine ligands, as well as genes related to periovulatory events, within the cumulus oocyte complex (COC) and follicle wall after a luteinizing hormone (LH) stimulus in cultured feline antral follicles; b) assess the immunolocalization of CCR2 and its main ligand (monocyte chemoattractant protein 1, MCP1) within the feline COC; and c) examine the direct effects of exogenous recombinant MCP1 on mRNA expression of the CCR2 receptor and MCP1 as well as key periovulatory genes in the COC, using a feline COC culture system. Both culture systems were developed by our laboratory and exhibit physiological response to gonadotropin stimuli. In summary, this study demonstrated mRNA expression of CCR2 receptor and its assessed ligands (MCP1, MCP2, MCP3 and MCP4) within the feline COC and follicle antral wall, and a significant increase in CCR2 mRNA by LH within the COC. Also, CCR2 and MCP1 immunoreactivity was observed in the oocyte and cumulus cells of the feline COC. Remarkably, this is the first report, in any species, describing a direct effect of the recombinant MCP1 in the CCR2/MCP1 system within the COC, by increasing the mRNA levels of key genes involved in the ovulatory cascade, as well as its own receptor CCR2. Together, these data suggest that CCR2 receptor signaling in the COC may regulate events critical for promoting cumulus oocyte expansion and/or oocyte maturation.//////////////////
Ovarian kisspeptin expression is related to age and to monocyte chemoattractant protein-1. Merhi Z et al. (2016) The objective of this study was to test the hypothesis that ovarian kisspeptin (kiss1) and its receptor (kiss1r) expression are affected by age, obesity, and the age- and obesity-related chemokine monocyte chemoattractant protein-1 (MCP-1). Ovaries from reproductive-aged and older C57BL/6J mice fed normal chow (NC) or high-fat (HF) diet, ovaries from age-matched young MCP-1 knockout and young control mice on NC, and finally, cumulus and mural granulosa cells (GCs) from women who underwent in vitro fertilization (IVF) were collected. Kiss1, kiss1r, anti-Mullerian hormone (AMH), and AMH receptor (AMHR-II) messenger RNA (mRNA) expression levels were quantified using real-time polymerase chain reaction (RT-PCR). In mouse ovaries, kiss1 and kiss1r mRNA levels were significantly higher in old compared to reproductive-aged mice, and diet-induced obesity did not alter kiss1 or kiss1r mRNA levels. Compared to young control mice, young MCP-1 knockout mice had significantly lower ovarian kiss1 mRNA but significantly higher AMH and AMHR-II mRNA levels. In human cumulus GCs, kiss1r mRNA levels were positively correlated with age but not with BMI. There was no expression of kiss1 mRNA in either cumulus or mural GCs. These data suggest a possible age-related physiologic role for the kisspeptinergic system in ovarian physiology. Additionally, the inflammatory MCP-1 may be associated with kiss1 and AMH genes, which are important in ovulation and folliculogenesis, respectively.//////////////////
Senturk et al. (1999) found found that MCP-1 expression and the number of macrophages increase with regression of the corpus luteum. MCP-1 is mostly expressed in blood vessel walls surrounding the corpus luteum and may play a role in the recruitment of macrophages to the corpus luteum during its regression.
Tsai et al. (1997) showed that a luteolytic dose of PGF2alpha or activation of PKC induced MCP-1 mRNA expression in bovine and ovine corpora lutea.
In rats MCP-1 staining and distribution was increased in corpora lutea during estrus; after the proestrus prolactin surge which induces luteolysis (Bowen et al., 1999).
BMP15 Prevents Cumulus Cell Apoptosis Through CCL2 and FBN1 in Porcine Ovaries. Zhai B 2013 et al.
Background: Bone morphogenetic protein-15 (BMP15) is a maternal gene necessary for mammalian reproduction. BMP15 expression increased in oocytes accompanied by follicle growth and development. The function and regulation mechanism of BMP15 in porcine cumulus cell apoptosis process is still unclear now. Methods: In this study, flow cytometry (FCM) was used to analyze the effects of BMP15 with different concentrations to cumulus cell apoptosis. High-throughput sequencing technology was carried out to screen regulatory genes linked closely with BMP15. In order to confirm the function of (MCP-1)/CCL2 and FBN1 in cumulus cell apoptosis, RNA interference (RNAi) method was used to inhibit the expression of (MCP-1)/CCL2 and FBN1. Apoptosis and proliferation of cumulus cell treated with siRNA transfection technology were measured by FCM, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, quantitative real time-PCR (RT-qPCR) and western blotting. Results: The results showed that the apoptosis levels of cumulus cell treated by BMP15 decreased significantly in a dose-dependent manner. The expression of related genes protein 1 (MCP-1)/CCL2 and fibrillin1 (FBN1) were both regulated by BMP15. After transfection, the proliferation of porcine cumulus cells increased significantly and apoptosis of cumulus cells was prevented while FBN1 was silenced after BMP15 treatment. The proliferation of cumulus cells decreased significantly and apoptosis rate of cumulus cells increased significantly while CCL2 was silenced. Conclusion: The results obtained in this study firstly demonstrated that CCL2 and FBN1 are important regulatory factors of BMP15 in preventing cumulus cell apoptosis in porcine ovaries.
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Arici et al., (1997) found a correlation between follicular fluid MCP-1 levels and follicular fluid or serum progesterone levels. MCP-1 mRNA and the protein were expressed in ovarian stromal and granulosa lutein cells in culture and were increased by interleukin-1 alpha and tumor necrosis factor-alpha in a time- and concentration-dependent manner. LH/hCG induced higher levels of MCP-1 mRNA expression and protein production in both cell cultures.
Ovarian localization
Luteal cells, Stromal cells, Follicular Fluid
Comment
Elevated Levels of Monocyte Chemotactic Protein-1 in the Follicular Fluid Reveals Different Populations among Women with Severe Endometriosis. Bouet PE et al. (2020) To determine if a modification of the cytokine profile occurs in the follicular fluid (FF) of women with endometriosis undergoing in vitro fertilization (IVF), we performed a prospective observational study from January 2018 to February 2019. In total, 87 women undergoing IVF were included: 43 for severe endometriosis-related infertility and 40 controls with other causes of infertility. The cytokine profile of the FF was determined by multiplex fluorescent-bead-based technology allowing the measurement of 59 cytokines. Monocyte Chemoattractant Protein 1 (MCP-1) was the only variable retained in the multivariate analysis. We identified two subgroups of patients in the endometriosis group: MCP-1-low group (n = 23), which had FF MCP-1 levels comparable to the control group, and MCP-1-high (n = 20), which had significantly higher FF levels. Only patients in the MCP-1-high group had a significantly altered cytokine profile in the FF, and had a significantly higher serum estradiol level (p = 0.002) and a significantly lower number of oocytes recovered (p = 0.01) compared to the MCP-1-low and the control group. Our study has shown an alteration of the oocyte microenvironment in women with endometriosis associated with high follicular fluid levels of MCP-1, allowing the identification of a subgroup of endometriosis patients with a potentially worse prognosis.//////////////////
Differential expression of inflammation-related genes in the ovarian stroma and granulosa cells of PCOS women. Johanna Schmidt JS 2013 et al.
Polycystic ovary syndrome (PCOS) is the most common female endocrine disorder. Ovarian changes in PCOS women are well characterised by ultrasound. However, the ovarian pathophysiology is not fully understood. The aim of this study was to characterise the expression, in both the central ovarian stroma and in granulosa cells (GC), of a number of genes, including several inflammation-related genes, which have been hypothesised to be involved in the pathophysiology of PCOS.Biopsies of the central ovarian stroma were obtained from PCOS women (Rotterdam criteria) and from normally ovulating women in follicular phase. Granulosa cells were retrieved from PCOS-women ornon-PCOS women, undergoing in vitro maturation (IVM). The expressions of 57 genes were analysed by quantitative-PCR using a Low-Density-Gene-Array. The main outcome measures were over-expression or under-expression of the specific genes.The results showed that in the central stroma of PCOS ovaries, five inflammation-related genes (CCL2, IL1R1, IL8, NOS2, TIMP1), the leukocyte marker CD45, the inflammation-related transcription factor RUNX2 and the growth factor AREG were under-expressed. The growth factor DUSP12 and the coagulation factor TFPI2 were over-expressed. In the GC of PCOS, all of the differentially expressed genes were over-expressed; the inflammation-related IL1B, IL8, LIF, NOS2 and PTGS2, the coagulation-related F3 and THBS1, the growth factors BMP6 and DUSP12, the permeability-related AQ3 and the growth-arrest-related GADD45A.In conclusion the results indicate major alterations in the local ovarian immune system of PCOS ovaries. This may have implications for the PCOS-related defects in the inflammation-like ovulatory process and for the susceptibility to acquire the inflammatory state of ovarian hyperstimulation syndrome.
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MCP-1 mRNA and the protein were expressed in ovarian stromal and granulosa lutein cells in culture (Aciri et al, 1997).
Concentrations of MCP-1 mRNA were detectable in ewes 2h after administration of a luteolytic dose of prostaglandin F2 alpha. In situ hybridization for MCP-1 mRNA combined with immunocytochemical labeling of tissue inhibitor of metalloproteinase-1 (TIMP-1) in large luteal cells indicated that MCP-1 was not expressed by large steroidogenic luteal cells during luteolysis (Haworth et al, 1998).Hosang et al. (1994) identified MCP-2 protein in porcine luteal cells.
Follicle stages
Corpus luteum
Comment
Invasion of the corpus luteum by macrophages is a characteristic of luteal regression. Monocyte chemotactic protein-1(MCP-1), a chemokine that recruits macrophages, is expressed in the rat corpus luteum where it increases in amount during luteolysis (Bowen et al., 1996).