Alternative titles; symbols
Other entities represented in this entry:
HGNC Approved Gene Symbol: CCL2
Cytogenetic location: 17q12 Genomic coordinates (GRCh38): 17:34,255,285-34,257,203 (from NCBI)
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
|---|---|---|---|---|
| 17q12 | {Coronary artery disease, modifier of} | 3 | ||
| {HIV-1, resistance to} | 609423 | 3 | ||
| {Mycobacterium tuberculosis, susceptibility to} | 607948 | 3 | ||
| {Spina bifida, susceptibility to} | 182940 | Autosomal dominant | 3 |
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. Southern blot analysis showed that it is present as a single gene in the genome and is conserved in several primates. MCP1 mRNA was induced in human peripheral blood mononuclear leukocytes by phytohemagglutinin (PHA), lipopolysaccharide, and interleukin-1 (see 147760), but not by IL2 (147680), TNF (191160), or IFN-gamma (147570). Sequence similarity suggested that MCP1 may be the human homolog of the mouse competence gene JE.
Furutani et al. (1989) isolated and sequenced cDNA clones having the identical nucleotide sequence and encoding a gene that they designated human monocyte chemotactic and activating factor (MCAF). The amino acid sequence deduced from the nucleotide sequence showed the primary structure of the MCAF precursor to be composed of a putative signal peptide sequence of 23 amino acid residues and a mature MCAF sequence of 76 amino acid residues. Robinson et al. (1989) reported the complete amino acid sequence of a monocyte chemotactic factor derived from a human glioma and called GDCF-2. The amino acid composition of this protein is the same as that of lymphocyte-derived chemotactic factor (LDCF), which is thought to account for monocyte accumulation in cellular immune reactions. The authors used Edman degradation and mass spectrometry to demonstrate that GDCF-2 consists of 76 amino acid residues, including 4 half-cysteines at positions 11, 12, 36, and 52.
By analysis of a panel of somatic cell hybrids, Mehrabian et al. (1991) localized the gene for monocyte chemotactic protein-1 (CCL2) to chromosome 17. By in situ hybridization, they localized the gene to 17q11.2-q21.1. By a combination of in situ hybridization and a study of somatic cell hybrids, Rollins et al. (1991) assigned the gene to 17q11.2-q12. They pointed out that CCL2 belongs to a family of cytokines which can be grouped into 2 subfamilies based on structure and chromosomal location, namely 17q and 4q. The cytokines on 4q are IL8 (146930), MGSA (155730), and macrophage inflammatory protein-2 (see 139110) (Wolpe et al., 1989).
Using flow cytometry, Corrigall et al. (2001) detected expression of a functional IL2 receptor of intermediate affinity composed solely of IL2RB (146710) and IL2RG (308380) on fibroblast-like synoviocytes (FLS) obtained from rheumatoid arthritis and osteoarthritis patients. Addition of recombinant IL2, IL1B (147720), or TNFA independently did not upregulate expression of the receptors on FLS, but IL2 or IL1B did significantly increase expression of intracellular tyrosine-phosphorylated proteins and the production of MCP1. Corrigall et al. (2001) proposed that MCP1 in the synovial membrane serves to recruit macrophages and perpetuate inflammation in the joints of patients with rheumatoid arthritis.
Aljada et al. (2001) investigated whether insulin (176730) inhibits the proinflammatory chemokine MCP1, which attracts leukocytes to inflamed sites and is regulated by NF-kappa-B (see 164011). Insulin was incubated with cultured human aortic endothelial cells at 0, 100, and 1,000 microU/mL. Intranuclear NF-kappa-B binding activity was suppressed by approximately 45% at 100 microU/mL and by 60% at 1,000 microU/mL. MCP1 mRNA expression was also suppressed by 47% at 100 microU/mL and by 79% at 1,000 microU/mL. The authors concluded that insulin at physiologically relevant concentrations exerts an inhibitory effect on the cardinal proinflammatory transcription factor NF-kappa-B and the proinflammatory chemokine MCP1; these effects suggest an antiinflammatory and potential antiatherogenic effect of insulin.
Sartipy and Loskutoff (2003) showed that insulin induces substantial expression and secretion of MCP1 both in vitro in insulin-resistant adipocytes and in vivo in insulin-resistant obese mice (ob/ob). Thus, MCP1 resembles other genes that remain sensitive to insulin in insulin-resistant states (e.g., PAI1, 173360). The hyperinsulinemia that frequently accompanies obesity and insulin resistance may therefore contribute to the altered expression of these and other genes in insulin target tissues. These and other results suggested that elevated MCP1 may induce adipocyte dedifferentiation and contribute to pathologic states associated with hyperinsulinemia and obesity, including type II diabetes (125853).
Schistosoma species (see 181460) are helminth parasites that are adept at manipulating the host immune system to allow tolerance of chronic worm infections without overt morbidity. This modulation of immunity by schistosomes prevents a range of immune-mediated diseases, including allergies and autoimmunity. Smith et al. (2005) identified a molecule produced by Schistosoma eggs, termed S. mansoni chemokine-binding protein (smCKBP), that bound several chemokines, including CCL2. SmCKBP blocked interaction of these chemokines with their receptors and thereby inhibited induction of inflammation. Smith et al. (2005) proposed that since smCKBP is unrelated to host proteins, it may have potential as an antiinflammatory agent.
Kanda et al. (2006) found increased abundance of Mcp1 mRNA in adipose tissue and Mcp1 protein in plasma in genetically obese diabetic (db/db) mice and in wildtype mice with obesity induced by a high-fat diet. Insulin resistance, hepatic steatosis, and macrophage accumulation in adipose tissue induced by a high-fat diet were reduced extensively in Mcp1 -/- mice compared with wildtype animals. Acute expression of a dominant-negative mutant of Mcp1 ameliorated insulin resistance in db/db mice and in wildtype mice fed a high-fat diet.
In a study of chemokine expression in fibroblasts from patients with systemic sclerosis (181750) and controls, Galindo et al. (2001) found that systemic sclerosis fibroblasts displayed increased constitutive expression of MCP1 mRNA and protein and showed a blunted response to oxidative stress. In systemic sclerosis skin sections, MCP1 expression was detected in fibroblasts, keratinocytes, and mononuclear cells, whereas it was undetectable in normal skin.
Using in situ hybridization and immunohistochemistry studies for MCP1 on skin biopsy specimens, Distler et al. (2001) found that MCP1 was expressed by fibroblasts, keratinocytes, and perivascular infiltrates throughout the skin, in involved as well as uninvolved areas, from 10 of 11 systemic sclerosis patients, whereas no expression of MCP1 was found in healthy controls. Stimulation with platelet-derived growth factor (PDGF; see 173430) resulted in a significant increase in MCP1 mRNA and protein. The chemotactic activity of peripheral blood mononuclear cells in systemic sclerosis fibroblast supernatants decreased when MCP1-blocking antibodies were added. No effect of recombinant MCP1 on the synthesis of type I collagen (see 120150) was observed. Distler et al. (2001) suggested that MCP1 may contribute to the initiation of inflammatory infiltrates in systemic sclerosis, possibly in response to stimulation by PDGF.
Qian et al. (2011) defined the origin of metastasis-associated macrophages by showing that Gr1-positive inflammatory monocytes are preferentially recruited to pulmonary metastases but not to primary mammary tumors in mice. This process also occurs for human inflammatory monocytes in pulmonary metastases of human breast cancer cells. The recruitment of these inflammatory monocytes, which express CCR2 (601267), the receptor for chemokine CCL2, as well as the subsequent recruitment of metastasis-associated macrophages and their interaction with metastasizing tumor cells, is dependent on CCL2 synthesized by both the tumor and the stroma. Inhibition of CCL2-CCR2 signaling blocked the recruitment of inflammatory monocytes, inhibited metastasis in vivo, and prolonged the survival of tumor-bearing mice. Depletion of tumor cell-derived CCL2 also inhibited metastatic seeding. Inflammatory monocytes promote the extravasation of tumor cells in a process that requires monocyte-derived vascular endothelial growth factor (VEGF; 192240). CCL2 expression and macrophage infiltration are correlated with poor prognosis and metastatic disease in human breast cancer. Qian et al. (2011) suggested that their data provide the mechanistic link between these 2 clinical associations.
Bonapace et al. (2014) reported a paradoxical effect of CCL2 in 4 syngeneic mouse models of metastatic breast cancer. Surprisingly, interruption of Ccl2 inhibition leads to an overshoot of metastases and accelerated death. This was the result of monocyte release from the bone marrow and enhancement of cancer cell mobilization from the primary tumor, as well as blood vessel formation and increased proliferation of metastatic cells in the lungs in an IL6 (147620)- and VEGFA-dependent manner. Notably, inhibition of Ccl2 and Il6 markedly reduced metastases and increased survival of the animals. CCL2 has been implicated in various neoplasias and adopted as a therapeutic target. However, Bonapace et al. (2014) concluded that their results prompt caution when considering anti-CCL2 agents as monotherapy in metastatic disease and highlight the tumor microenvironment as a critical determinant of successful antimetastatic therapy.
Modi et al. (2003) identified 3 SNPs that formed a 31-kb haplotype (H7; see 158105.0001) spanning the CCL2-CCL7 (158106)-CCL11 (601156) gene cluster on chromosome 17q. The SNPs and the H7 haplotype were significantly associated with protection from HIV-1 infection (see 609423).
Spina bifida (182940) is one of the most common congenital malformations. Early first trimester hyperthermia, caused by infection/fever or use of hot tubs/saunas, is associated with a 2-fold increase in the risk of spina bifida (see Chambers et al., 1998). This suggests that processes related to inflammation and elevated body temperature, in particular signaling by molecules such as chemokines, may be involved in the etiology of spina bifida. A polymorphism, A(-2518)G (158105.0003), in the CCL2 gene differentially controls the level of MCP1 protein that monocytes export following treatment with interleukin-1-beta (147720) in vitro (Rovin et al., 1999). Cells with the homozygous AA genotype produce significantly less MCP1 than do cells with either the AG or GG genotype (Rovin et al., 1999). Furthermore, genotype for the A(-2518)G polymorphism is associated with severity of coronary artery disease (CAD) in those with established CAD (Szalai et al., 2001) and the progression to CAD in patients with HIV (Alonso-Villaverde et al., 2004). Jensen et al. (2006) hypothesized, therefore, that the CCL2 A(-2518)G promoter polymorphism would be a maternal genetic risk factor for spina bifida and, specifically, that the maternal homozygous AA genotype, by mounting a less vigorous systemic and/or local response to infection, would confer excess risk. They tested the hypothesis in 469 families in which at least 1 member had spina bifida. Their finding that the maternal genotype for the CCL2 A(-2518)G polymorphism is associated with spina bifida was the first involving an immune/inflammation related gene.
Flores-Villanueva et al. (2005) found an increased risk of developing tuberculosis (TB; see 607948) in Mexicans and Koreans heterozygous or homozygous for MCP1 -2518G (rs1024611) compared with those homozygous for -2518A. ELISA analysis showed that TB patients homozygous for -2518G had the highest plasma levels of MCP1 and the lowest plasma levels of IL12p40 (IL12B; 161561), and these values were negatively correlated. Stimulation of monocytes from healthy -2518G homozygotes with M. tuberculosis antigens also yielded higher MCP1 and lower IL12p40 compared with healthy -2518A homozygotes. Addition of anti-MCP1 increased IL12 production by -2518G homozygotes, whereas addition of MCP1 reduced IL12 production by -2518A homozygotes. Flores-Villanueva et al. (2005) concluded that those with the MCP1 -2518GG genotype produce high concentration of MCP1, which inhibits IL12p40 production in response to M. tuberculosis and increases the likelihood of TB infection progressing to active disease.
The results of Thye et al. (2009) did not support an association of MCP1 -12581 with TB.
Lu et al. (1998) generated mice with targeted disruption of the MCP1 gene. Despite normal numbers of circulating leukocytes and resident macrophages, Mcp1 -/- mice were specifically unable to recruit monocytes 72 hours after intraperitoneal thioglycollate administration. Similarly, accumulation of F4/80+ monocytes in delayed-type hypersensitivity lesions was impaired, although the swelling response was normal. Development of secondary pulmonary granulomata in response to Schistosoma mansoni eggs was blunted in Mcp1 -/- mice, as was expression of IL4 (147780), IL5 (147850), and interferon-gamma in splenocytes. In contrast, Mcp1 -/- mice were indistinguishable from wildtype mice in their ability to clear Mycobacterium tuberculosis. These data indicated that MCP1 is uniquely essential for monocyte recruitment in several inflammatory models in vivo and influences expression of cytokines related to T helper responses.
Recruitment of blood monocytes into the arterial subendothelium is one of the earliest steps in atherogenesis. MCP1, a CC chemokine, is one likely signal involved in this process. To test the role of MCP1 in atherogenesis, Gu et al. (1998) generated low density lipoprotein (LDL) receptor-deficient mice that were also deficient for Mcp1 and fed them a high cholesterol diet. Despite having the same amount of total and fractionated serum cholesterol as LDL receptor-deficient mice with wildtype Mcp1 alleles, LDL receptor/Mcp1-deficient mice had 83% less lipid deposition throughout their aortas. Consistent with the monocyte chemoattractant properties of MCP1, compound-deficient mice also had fewer macrophages in their aortic walls. Thus, MCP1 plays a unique and crucial role in the initiation of atherosclerosis. Comparable findings were reported by Gosling et al. (1999), who reported that absence of the Mcp1 gene in transgenic mice overexpressing human apolipoprotein B provided dramatic protection from macrophage recruitment and atherosclerotic lesion formation, without altering lipoprotein metabolism.
Gu et al. (2000) demonstrated that Mcp1-deficient mice were unable to mount type 2 helper cell (TH2) responses. Lymph node cells from immunized Mcp1 -/- mice synthesized extremely low levels of interleukin-4, interleukin-5, and interleukin-10 (124092) but normal amounts of interferon-gamma and interleukin-2. Consequently, these mice did not accomplish the immunoglobulin subclass switch that is characteristic of TH2 responses and were resistant to Leishmania major. The observed effects were direct rather than due to abnormal cell migration, because the trafficking of naive T cells is undisturbed in Mcp1 -/- mice despite the presence of Mcp1-expressing cells in secondary lymphoid organs of wildtype mice. Gu et al. (2000) concluded that MCP1 influences both innate immunity, through effects on monocytes, and adaptive immunity, through control of T helper cell polarization.
Ambati et al. (2003) found that mice lacking either Mcp1 or its receptor, Ccr2 (601267), developed cardinal features of age-related macular degeneration (ARMD; see, e.g., 153800), including accumulation of lipofuscin in, and drusen beneath, the retinal pigmented epithelium (RPE), photoreceptor atrophy, and choroidal neovascularization. In addition there was an age-related accumulation of complement components and IgG in the RPE of the knockout mice, perhaps reflecting dysfunction in macrophage recruitment.
Zhou et al. (2006) showed in vitro that MCP1 binding to CCR2 induced a transcription factor ZC3H12A (610562) that is involved in apoptosis. In transgenic mice expressing MCP1 in cardiomyocytes, which is a model of heart failure following cardiac inflammation, they found increased ZC3H12A expression, increased cell death, and accumulation of ZC3H12A protein in myocardial vacuoles, characteristic of both human and mouse heart failure.
The chemokine MCP1 had been shown to be a mediator of macrophage-related neural damage in models of 2 distinct inherited neuropathies, Charcot-Marie-Tooth (CMT) 1A (118220) and 1B (118200). In mice deficient in the gap junction protein connexin-32 (Cx32def; see 304040), Groh et al. (2010) investigated the role of the chemokine in macrophage immigration and neural damage by crossbreeding Cx32def mice with MCP1 knockout mutants. In Cx32def mutants typically expressing increased levels of MCP1, macrophage numbers were strongly elevated, caused by an MCP1-mediated influx of hematogenous macrophages. In contrast, heterozygous deletion of MCP1 led to reduced numbers of phagocytosing macrophages and an alleviation of demyelination. Whereas alleviated demyelination was transient, axonal damage was persistently improved and even robust axonal sprouting was detectable at 12 months. Other axon-related features were alleviated electrophysiologic parameters, reduced muscle denervation and atrophy, and increased muscle strength. Similar to models for CMT1A and CMT1B, MEK-ERK (see 176872; see 601795) signaling mediated MCP1 expression in Cx32-deficient Schwann cells. Blocking this pathway by the inhibitor CI-1040 caused reduced MCP1 expression, attenuation of macrophage increase, and amelioration of myelin- and axon-related alterations. Groh et al. (2010) concluded that attenuation of MCP1 upregulation by inhibiting ERK phosphorylation could be a promising approach to treat CMT1X and other inherited peripheral neuropathies.
Modi et al. (2003) genotyped 9 SNPs spanning the CCL2-CCL7 (158106)-CCL11 (601156) gene cluster on chromosome 17q in more than 3,000 DNA samples from 5 AIDS cohorts (see 609423). Extensive linkage disequilibrium was observed, particularly for 3 SNPs, -2136T in the CCL2 promoter, 767G in intron 1 of the CCL2 gene (158105.0002), and -1385A in the CCL11 promoter (601156.0001), that formed a 31-kb haplotype (H7) containing the 3 genes. The frequencies of these 3 SNPs and the H7 haplotype were significantly elevated in uninfected individuals repeatedly exposed to HIV-1 through high-risk sexual behavior or contaminated blood products. Since these chemokines do not bind the primary HIV-1 coreceptors CCR5 (601373) or CXCR4 (162643), Modi et al. (2003) proposed that the influence of the H7 haplotype on HIV-1 transmission may result from activation of the immune system rather than receptor blockage.
See 158105.0001 and Modi et al. (2003).
Jensen et al. (2006) related maternal homozygosity for the A allele of the A(-2518)G promoter polymorphism of the CCL2 gene (rs1024611) to susceptibility to spina bifida (182940). The investigation was initiated because of the relationship between maternal inflammation and elevated body temperature to the development of spina bifida. The same polymorphism had been associated with the severity of coronary artery disease in patients with established CAD (Szalai et al., 2001) and a progression to CAD in HIV patients (Alonso-Villaverde et al., 2004).
Flores-Villanueva et al. (2005) found that Mexicans heterozygous or homozygous for -2518G had a 2.3- and 5.4-fold increased risk of developing active pulmonary tuberculosis (607948), respectively. Among Korean patients, the increased risk was 2.8- and 6.9-fold higher, respectively.
Thye et al. (2009) determined the -2518 genotype and additional MCP1 variants in more than 2,000 cases with pulmonary TB and more than 2,300 healthy controls and 332 affected nuclear families from Ghana, West Africa, and more than 1,400 TB patients and more than 1,500 controls from Russia. In contrast to the report of Flores-Villanueva et al. (2005), MCP1 -2518G was significantly associated with resistance to TB in cases versus controls (odds ratio (OR) 0.81, corrected P value (Pcorr) = 0.0012) and nuclear families (OR 0.72, Pcorr = 0.04) and not with disease susceptibility, whereas in the Russian sample no evidence of association was found (P = 0.86). These and other results did not support an association of MCP1 -2518 with TB. In the Ghanaian population, 8 additional MCP1 polymorphisms were genotyped. MCP1 -362C was associated with resistance to TB in the case-control collection (OR 0.83, Pcorr = 0.00017) and in the affected families (OR 0.7, Pcorr = 0.004). Linkage disequilibrium (LD) and logistic regression analyses indicated that, in Ghanaians, the effect was due exclusively to the MCP1 -362 variant, whereas the effect of -2518 may in part be explained by its LD with -362.
Aljada, A., Ghanim, H., Saadeh, R., Dandona, P. Insulin inhibits NF-kappa-B and MCP-1 expression in human aortic endothelial cells. J. Clin. Endocr. Metab. 86: 450-453, 2001. [PubMed: 11232040] [Full Text: https://doi.org/10.1210/jcem.86.1.7278]
Alonso-Villaverde, C., Coll, B., Parra, S., Montero, M., Calvo, N., Tous, M., Joven, J., Masana, L. Atherosclerosis in patients infected with HIV is influenced by a mutant monocyte chemoattractant protein-1 allele. Circulation 110: 2204-2209, 2004. [PubMed: 15466648] [Full Text: https://doi.org/10.1161/01.CIR.0000143835.95029.7D]
Ambati, J., Anand, A., Fernandez, S., Sakurai, E., Lynn, B. C., Kuziel, W. A., Rollins, B. J., Ambati, B. K. An animal model of age-related macular degeneration in senescent Ccl-2- or Ccr-2-deficient mice. Nature Med. 9: 1390-1397, 2003. [PubMed: 14566334] [Full Text: https://doi.org/10.1038/nm950]
Bonapace, L., Coissieux, M.-M., Wyckoff, J., Mertz, K. D., Varga, Z., Junt, T., Bentires-Alij, M. Cessation of CCL2 inhibition accelerates breast cancer metastasis by promoting angiogenesis. Nature 515: 130-133, 2014. [PubMed: 25337873] [Full Text: https://doi.org/10.1038/nature13862]
Chambers, C. D., Johnson, K. A., Dick, L. M., Felix, R. J., Jones, K. L. Maternal fever and birth outcome: a prospective study. Teratology 58: 251-257, 1998. [PubMed: 9894674] [Full Text: https://doi.org/10.1002/(SICI)1096-9926(199812)58:6<251::AID-TERA6>3.0.CO;2-L]
Corrigall, V. M., Arastu, M., Khan, S., Shah, C., Fife, M., Smeets, T., Tak, P.-P., Panayi, G. S. Functional IL-2 receptor beta (CD122) and gamma (CD132) chains are expressed by fibroblast-like synoviocytes: activation by IL-2 stimulates monocyte chemoattractant protein-1 production. J. Immun. 166: 4141-4147, 2001. [PubMed: 11238664] [Full Text: https://doi.org/10.4049/jimmunol.166.6.4141]
Distler, O., Pap, T., Kowal-Bielecka, O., Meyringer, R., Guiducci, S, Landthaler, M., Scholmerich, J., Michel, B. A., Gay, R. E., Matucci-Cerinic, M., Gay, S., Muller-Ladner, U. Overexpression of monocyte chemoattractant protein 1 in systemic sclerosis: role of platelet-derived growth factor and effects on monocyte chemotaxis and collagen synthesis. Arthritis Rheum. 44: 2665-2678, 2001. [PubMed: 11710722] [Full Text: https://doi.org/10.1002/1529-0131(200111)44:11<2665::aid-art446>3.0.co;2-s]
Flores-Villanueva, P. O., Ruiz-Morales, J. A., Song, C.-H., Flores, L. M., Jo, E.-K., Montano, M., Barnes, P. F., Selman, M., Granados, J. A functional promoter polymorphism in monocyte chemoattractant protein-1 is associated with increased susceptibility to pulmonary tuberculosis. J. Exp. Med. 202: 1649-1658, 2005. [PubMed: 16352737] [Full Text: https://doi.org/10.1084/jem.20050126]
Furutani, Y., Nomura, H., Notake, M., Oyamada, Y., Fukui, T., Yamada, M., Larsen, C. G., Oppenheim, J. J., Matsushima, K. Cloning and sequencing of the cDNA for human monocyte chemotactic and activating factor (MCAF). Biochem. Biophys. Res. Commun. 159: 249-255, 1989. [PubMed: 2923622] [Full Text: https://doi.org/10.1016/0006-291x(89)92430-3]
Galindo, M., Santiago, B., Rivero, M., Rullas, J., Alcami, J., Pablos, J. L. Chemokine expression by systemic sclerosis fibroblasts: abnormal regulation of monocyte chemoattractant protein 1 expression. Arthritis Rheum. 44: 1382-1386, 2001. [PubMed: 11407698] [Full Text: https://doi.org/10.1002/1529-0131(200106)44:6<1382::AID-ART231>3.0.CO;2-T]
Gosling, J., Slaymaker, S., Gu, L., Tseng, S., Zlot, C. H., Young, S. G., Rollins, B. J., Charo, I. F. MCP-1 deficiency reduces susceptibility to atherosclerosis in mice that overexpress human apolipoprotein B. J. Clin. Invest. 103: 773-778, 1999. [PubMed: 10079097] [Full Text: https://doi.org/10.1172/JCI5624]
Groh, J., Heinl, K., Kohl, B., Wessig, C., Greeske, J., Fischer, S., Martini, R. Attenuation of MCP-1/CCL2 expression ameliorates neuropathy in a mouse model for Charcot-Marie-Tooth 1X. Hum. Molec. Genet. 19: 3530-3543, 2010. [PubMed: 20591826] [Full Text: https://doi.org/10.1093/hmg/ddq269]
Gu, L., Okada, Y., Clinton, S. K., Gerard, C., Sukhova, G. K., Libby, P., Rollins, B. J. Absence of monocyte chemoattractant protein-1 reduces atherosclerosis in low density lipoprotein receptor-deficient mice. Molec. Cell 2: 275-281, 1998. [PubMed: 9734366] [Full Text: https://doi.org/10.1016/s1097-2765(00)80139-2]
Gu, L., Tseng, S., Horner, R. M., Tam, C., Loda, M., Rollins, B. J. Control of TH2 polarization by the chemokine monocyte chemoattractant protein-1. Nature 404: 407-411, 2000. [PubMed: 10746730] [Full Text: https://doi.org/10.1038/35006097]
Jensen, L. E., Etheredge, A. J., Brown, K. S., Mitchell, L. E., Whitehead, A. S. Maternal genotype for the monocyte chemoattractant protein 1 A(-2518)G promoter polymorphism is associated with the risk of spina bifida in offspring. Am. J. Med. Genet. 140A: 1114-1118, 2006. [PubMed: 16596675] [Full Text: https://doi.org/10.1002/ajmg.a.31212]
Kanda, H., Tateya, S., Tamori, Y., Kotani, K., Hiasa, K., Kitazawa, R., Kitazawa, S., Miyachi, H., Maeda, S., Egashira, K., Kasuga, M. MCP-1 contributes to macrophage infiltration into adipose tissue, insulin resistance, and hepatic steatosis in obesity. J. Clin. Invest. 116: 1494-1505, 2006. [PubMed: 16691291] [Full Text: https://doi.org/10.1172/JCI26498]
Lu, B., Rutledge, B. J., Gu, L., Fiorillo, J., Lukacs, N. W., Kunkel, S. L., North, R., Gerard, C., Rollins, B. J. Abnormalities in monocyte recruitment and cytokine expression in monocyte chemoattractant protein 1-deficient mice. J. Exp. Med. 187: 601-608, 1998. [PubMed: 9463410] [Full Text: https://doi.org/10.1084/jem.187.4.601]
Mehrabian, M., Sparkes, R. S., Mohandas, T., Fogelman, A. M., Lusis, A. J. Localization of monocyte chemotactic protein-1 gene (SCYA2) to human chromosome 17q11.2-q21.1. Genomics 9: 200-203, 1991. [PubMed: 2004761] [Full Text: https://doi.org/10.1016/0888-7543(91)90239-b]
Modi, W. S., Goedert, J. J., Strathdee, S., Buchbinder, S., Detels, R., Donfield, S., O'Brien, S. J., Winkler, C. MCP-1-MCP-3-eotaxin gene cluster influences HIV-1 transmission. AIDS 17: 2357-2365, 2003. [PubMed: 14571188] [Full Text: https://doi.org/10.1097/00002030-200311070-00011]
Qian, B.-Z., Li, J., Zhang, H., Kitamura, T., Zhang, J., Campion, L. R., Kaiser, E. A., Snyder, L. A., Pollard, J. W. CCL2 recruits inflammatory monocytes to facilitate breast-tumour metastasis. Nature 475: 222-225, 2011. [PubMed: 21654748] [Full Text: https://doi.org/10.1038/nature10138]
Robinson, E. A., Yoshimura, T., Leonard, E. J., Tanaka, S., Griffin, P. R., Shabanowitz, J., Hunt, D. F., Appella, E. Complete amino acid sequence of a human monocyte chemoattractant, a putative mediator of cellular immune reactions. Proc. Nat. Acad. Sci. 86: 1850-1854, 1989. [PubMed: 2648385] [Full Text: https://doi.org/10.1073/pnas.86.6.1850]
Rollins, B. J., Morton, C. C., Ledbetter, D. H., Eddy, R. L., Jr., Shows, T. B. Assignment of the human small inducible cytokine A2 gene, SCYA2 (encoding JE or MCP-1), to 17q11.2-12: evolutionary relatedness of cytokines clustered at the same locus. Genomics 10: 489-492, 1991. [PubMed: 2071154] [Full Text: https://doi.org/10.1016/0888-7543(91)90338-f]
Rovin, B. H., Lu, L., Saxena, R. A novel polymorphism in the MCP-1 gene regulatory region that influences MCP-1 expression. Biochem. Biophys. Res. Commun. 259: 344-348, 1999. [PubMed: 10362511] [Full Text: https://doi.org/10.1006/bbrc.1999.0796]
Sartipy, P., Loskutoff, D. J. Monocyte chemoattractant protein 1 in obesity and insulin resistance. Proc. Nat. Acad. Sci. 100: 7265-7270, 2003. [PubMed: 12756299] [Full Text: https://doi.org/10.1073/pnas.1133870100]
Smith, P., Fallon, R. E., Mangan, N. E., Walsh, C. M., Saraiva, M., Sayers, J. R., McKenzie, A. N. J., Alcami, A., Fallon, P. G. Schistosoma mansoni secretes a chemokine binding protein with antiinflammatory activity. J. Exp. Med. 202: 1319-1325, 2005. [PubMed: 16301741] [Full Text: https://doi.org/10.1084/jem.20050955]
Szalai, C., Duba, J., Prohaszka, Z., Kalina, A., Szabo, T., Nagy, B., Horvath, L., Csaszar, A. Involvement of polymorphisms in the chemokine system in the susceptibility for coronary artery disease (CAD). Coincidence of elevated Lp(a) and MCP-1 -2518 G/G genotype in CAD patients. Atherosclerosis 158: 233-239, 2001. [PubMed: 11500196] [Full Text: https://doi.org/10.1016/s0021-9150(01)00423-3]
Thye, T., Nejentsev, S., Intemann, C. D., Browne, E. N., Chinbuah, M. A., Gyapong, J., Osei, I., Owusu-Dabo, E., Zeitels, L. R., Herb, F., Horstmann, R. D., Meyer, C. G. MCP-1 promoter variant -362C associated with protection from pulmonary tuberculosis in Ghana, West Africa. Hum. Molec. Genet. 18: 381-388, 2009. [PubMed: 18940815] [Full Text: https://doi.org/10.1093/hmg/ddn352]
Wolpe, S. D., Sherry, B., Juers, D., Davatelis, G., Yurt, R. W., Cerami, A. Identification and characterization of macrophage inflammatory protein 2. Proc. Nat. Acad. Sci. 86: 612-616, 1989. [PubMed: 2643119] [Full Text: https://doi.org/10.1073/pnas.86.2.612]
Yoshimura, T., Yuhki, N., Moore, S. K., Appella, E., Lerman, M. I., Leonard, E. J. Human monocyte chemoattractant protein-1 (MCP-1): full-length cDNA cloning, expression in mitogen-stimulated blood mononuclear leukocytes, and sequence similarity to mouse competence gene JE. FEBS Lett. 244: 487-493, 1989. [PubMed: 2465924] [Full Text: https://doi.org/10.1016/0014-5793(89)80590-3]
Zhou, L., Azfer, A., Niu, J., Graham, S., Choudhury, M., Adamski, F. M., Younce, C., Binkley, P. F., Kolattukudy, P. E. Monocyte chemoattractant protein-1 induces a novel transcription factor that causes cardiac myocyte apoptosis and ventricular dysfunction. Circ. Res. 98: 1177-1185, 2006. [PubMed: 16574901] [Full Text: https://doi.org/10.1161/01.RES.0000220106.64661.71]