Genomes and Genes
Gene Symbol: Ccl4
Description: chemokine (C-C motif) ligand 4
Alias: AT744.1, Act-2, MIP-1B, Mip1b, Scya4, C-C motif chemokine 4, ACT2, MIP-1-beta, SIS-gamma, immune activation protein 2, macrophage inflammatory protein 1-beta, small-inducible cytokine A4
- Wang M, Jeng K, Shih P. Differential expression and regulation of macrophage inflammatory protein (MIP)-1alpha and MIP-2 genes by alveolar and peritoneal macrophages in LPS-hyporesponsive C3H/HeJ mice. Cell Immunol. 2000;204:88-95 pubmed..IFN-gamma suppressed the LPS-induced MIP-1alpha release but enhanced the LPS-induced MIP-2 secretion in both macrophages. These results show that the chemokine production was induced and regulated differentially in AMphi; and PMphi;. ..
- Yahiaoui L, Gvozdic D, Danialou G, Mack M, Petrof B. CC family chemokines directly regulate myoblast responses to skeletal muscle injury. J Physiol. 2008;586:3991-4004 pubmed publisher..chemoattractant protein-1 (MCP-1; CCL2), macrophage inflammatory protein-1alpha (MIP-1alpha; CCL3) or MIP-1beta (CCL4)...
- Dorner B, Scheffold A, Rolph M, Huser M, Kaufmann S, Radbruch A, et al. MIP-1alpha, MIP-1beta, RANTES, and ATAC/lymphotactin function together with IFN-gamma as type 1 cytokines. Proc Natl Acad Sci U S A. 2002;99:6181-6 pubmed
- Cohen Tannoudji M, Vandormael Pournin S, Le Bras S, Coumailleau F, Babinet C, Baldacci P. A 2-Mb YAC/BAC-based physical map of the ovum mutant (Om) locus region on mouse chromosome 11. Genomics. 2000;68:273-82 pubmed..Two other genes (Rad51l3 and Schlafen 2) and one EST (D11Wsu78e) were also mapped in the Om region. This integrated map provides support for the identification of additional candidate genes for the DDK syndrome. ..
- Bermingham J, Arden K, Naumova A, Sapienza C, Viars C, Fu X, et al. Chromosomal localization of mouse and human genes encoding the splicing factors ASF/SF2 (SFRS1) and SC-35 (SFRS2). Genomics. 1995;29:70-9 pubmed..Mapping of Sfrs1 using F1 hybrid backcross mice between the strains C57BL/6 and DDK places Sfrs1 very near the marker D11Mit38 and indicates that the ASF/SF2 gene is closely linked to the Ovum mutant locus. ..
- Meagher C, Arreaza G, Peters A, Strathdee C, Gilbert P, Mi Q, et al. CCL4 protects from type 1 diabetes by altering islet beta-cell-targeted inflammatory responses. Diabetes. 2007;56:809-17 pubmedWe previously reported that interleukin (IL)-4 treatment of nonobese diabetic (NOD) mice elevates intrapancreatic CCL4 expression and protects from type 1 diabetes...
- Mello Coelho V, Bunbury A, Rangel L, Giri B, Weeraratna A, Morin P, et al. Fat-storing multilocular cells expressing CCR5 increase in the thymus with advancing age: potential role for CCR5 ligands on the differentiation and migration of preadipocytes. Int J Med Sci. 2009;7:1-14 pubmed..We verified that the expression of CCR5 and its ligands, CCL3, CCL4 and CCL5, were increased in the thymus with age...
- Gill B, Jaramillo A, Ma L, Laupland K, Delovitch T. Genetic linkage of thymic T-cell proliferative unresponsiveness to mouse chromosome 11 in NOD mice. A possible role for chemokine genes. Diabetes. 1995;44:614-9 pubmed..This finding raises the possibility that a beta-chemokine(s) may regulate T-cell unresponsiveness as well as diabetes susceptibility in NOD mice. ..
- Williams A, JosÃ© R, Brown J, Chambers R. Enhanced inflammation in aged mice following infection with Streptococcus pneumoniae is associated with decreased IL-10 and augmented chemokine production. Am J Physiol Lung Cell Mol Physiol. 2015;308:L539-49 pubmed publisher..pneumoniae infection, compared with young mice, but increased levels of the chemokines CXCL9, CXCL12, CCL3, CCL4, CCL5, CCL11, and CCL17. Moreover, levels of IL-10 were significantly lower in aged animals...
- Vroon A, Heijnen C, Lombardi M, Cobelens P, Mayor F, Caron M, et al. Reduced GRK2 level in T cells potentiates chemotaxis and signaling in response to CCL4. J Leukoc Biol. 2004;75:901-9 pubmed..we investigated whether reduced GRK2 expression changes the chemotactic response of T cells to the chemokines CCL3, CCL4, and CCL5...
- Mendes da Cruz D, Silva J, Cotta de Almeida V, Savino W. Altered thymocyte migration during experimental acute Trypanosoma cruzi infection: combined role of fibronectin and the chemokines CXCL12 and CCL4. Eur J Immunol. 2006;36:1486-93 pubmed..Here, we analyzed the expression and role of selected chemokines (CXCL12 and CCL4) and their receptors (CXCR4 and CCR5) in regulating thymocyte migration in conjunction with extracellular matrix ..
- Khuu C, Barrozo R, Hai T, Weinstein S. Activating transcription factor 3 (ATF3) represses the expression of CCL4 in murine macrophages. Mol Immunol. 2007;44:1598-605 pubmedAcute expression of macrophage inflammatory protein-1 beta (also known as CCL4) promotes beneficial leukocyte recruitment to infected tissues, but chronic expression of this chemokine contributes to inflammatory disease...
- Fang L, Izumi K, Lai K, Liang L, Li L, Miyamoto H, et al. Infiltrating macrophages promote prostate tumorigenesis via modulating androgen receptor-mediated CCL4-STAT3 signaling. Cancer Res. 2013;73:5633-46 pubmed publisher..and that induction involves the alteration of signaling of macrophage androgen receptor (AR)-inflammatory chemokine CCL4-STAT3 activation as well as epithelial-to-mesenchymal transition and downregulation of p53/PTEN tumor suppressors...
- Yoon K, de Paiva C, Qi H, Chen Z, Farley W, Li D, et al. Expression of Th-1 chemokines and chemokine receptors on the ocular surface of C57BL/6 mice: effects of desiccating stress. Invest Ophthalmol Vis Sci. 2007;48:2561-9 pubmed..Desiccating stress potently stimulates the expression of Th-1 cell-attracting chemokines and chemokine receptors on the ocular surface of C57BL/6 mice. ..
- Fukuda S, Hanano Y, Iio M, Miura R, Yoshie O, Nomiyama H. Genomic organization of the genes for human and mouse CC chemokine LEC. DNA Cell Biol. 1999;18:275-83 pubmed..Southern blot analysis revealed that the sequence isolated from the BAC clone was the only one hybridizing with human LEC cDNA in the mouse genome. Therefore, mice may have only an LEC pseudogene. ..
- Rangel Santiago J, Baay Guzman G, Durán Padilla M, Lopez Bochm K, Garcia Romero B, Hernandez Cueto D, et al. A novel role of Yin-Yang-1 in pulmonary tuberculosis through the regulation of the chemokine CCL4. Tuberculosis (Edinb). 2016;96:87-95 pubmed publisher..The aim of this study was to elucidate the role of YY1 in the regulation of CCL4 and its implication in TB. We determined whether YY1 regulates CCL4 using reporter plasmids, ChIP and siRNA assays...
- Post T, Bozic C, Rothenberg M, Luster A, Gerard N, Gerard C. Molecular characterization of two murine eosinophil beta chemokine receptors. J Immunol. 1995;155:5299-305 pubmed..Murine MIP-1 alpha was found to be a potent chemoattractant for murine eosinophils. Our findings suggest that the murine MIP-1 alpha ligand/receptor system is an important mediator of murine eosinophil trafficking. ..
- Sasaki S, Baba T, Nishimura T, Hayakawa Y, Hashimoto S, Gotoh N, et al. Essential roles of the interaction between cancer cell-derived chemokine, CCL4, and intra-bone CCR5-expressing fibroblasts in breast cancer bone metastasis. Cancer Lett. 2016;378:23-32 pubmed publisher..4T1.3 clone displayed an enhanced expression of a chemokine, CCL4, but not its specific receptor, CCR5. CCL4 shRNA-transfection of 4T1...
- Bao L, Zhu Y, Zhu J, Lindgren J. Decreased IgG production but increased MIP-1beta expression in collagen-induced arthritis in C-C chemokine receptor 5-deficient mice. Cytokine. 2005;31:64-71 pubmed..Overproduction of MIP-1beta in CCR5-deficient mice after CII-immunization may contribute partially to the occurrence of arthritis. ..
- Brown K, Zurawski S, Mosmann T, Zurawski G. A family of small inducible proteins secreted by leukocytes are members of a new superfamily that includes leukocyte and fibroblast-derived inflammatory agents, growth factors, and indicators of various activation processes. J Immunol. 1989;142:679-87 pubmed..One of the small, inducible, secreted proteins has a predicted mature N terminus identical to that of the previously described macrophage inflammatory protein. ..
- Walmsley S, Print C, Farahi N, Peyssonnaux C, Johnson R, Cramer T, et al. Hypoxia-induced neutrophil survival is mediated by HIF-1alpha-dependent NF-kappaB activity. J Exp Med. 2005;201:105-15 pubmed..In addition, we identify macrophage inflammatory protein-1beta as a novel hypoxia-induced neutrophil survival factor. ..
- Irving S, Zipfel P, Balke J, McBride O, Morton C, Burd P, et al. Two inflammatory mediator cytokine genes are closely linked and variably amplified on chromosome 17q. Nucleic Acids Res. 1990;18:3261-70 pubmed..These genes are all located on chromosome 17 in bands q11-q21, the region implicated in von Recklinghausen neurofibromatosis (NF1) and in acute promyelocytic leukemia (AML-M3). ..
- Villegas Mendez A, Gwyer Findlay E, de Souza J, Grady L, Saris C, Lane T, et al. WSX-1 signalling inhibits CD4? T cell migration to the liver during malaria infection by repressing chemokine-independent pathways. PLoS ONE. 2013;8:e78486 pubmed publisher..Although CCL4 and CCL5 expression was higher in livers of infected WSX-1(-/-) mice than infected WT mice, and hepatic CD4? T ..
- Jing H, Vassiliou E, Ganea D. Prostaglandin E2 inhibits production of the inflammatory chemokines CCL3 and CCL4 in dendritic cells. J Leukoc Biol. 2003;74:868-79 pubmed..In this study we report that exogenous PGE2 inhibits CCL3 (MIP-1alpha) and CCL4 (MIP-1beta) expression and release from dendritic cells stimulated with either lipopolysaccharide (LPS), a TLR4 ..
- Kim S, Kim B, Lee S, Eo S, Yun Y, Kim C, et al. 27-Hydroxycholesterol and 7alpha-hydroxycholesterol trigger a sequence of events leading to migration of CCR5-expressing Th1 lymphocytes. Toxicol Appl Pharmacol. 2014;274:462-70 pubmed publisher..A high cholesterol diet resulted in enhanced expression of CCR5 ligands, including CCL3 and CCL4, but not of proatherogenic CXCR3 ligands, in atherosclerotic arteries of ApoE(-/-) mice...
- Widmer U, Manogue K, Cerami A, Sherry B. Genomic cloning and promoter analysis of macrophage inflammatory protein (MIP)-2, MIP-1 alpha, and MIP-1 beta, members of the chemokine superfamily of proinflammatory cytokines. J Immunol. 1993;150:4996-5012 pubmed
- van Driel B, Liao G, Romero X, O Keeffe M, Wang G, Faubion W, et al. Signaling lymphocyte activation molecule regulates development of colitis in mice. Gastroenterology. 2012;143:1544-1554.e7 pubmed publisher..Antibodies that inhibit Slamf1 reduce colitis in mice, so human SLAMF1 might be a therapeutic target for inflammatory bowel disease. ..
- Ross R, Ross X, Ghadially H, Lahr T, Schwing J, Knop J, et al. Mouse langerhans cells differentially express an activated T cell-attracting CC chemokine. J Invest Dermatol. 1999;113:991-8 pubmed..Thus, production of this chemokine by dendritic cells may be essential for the establishment and amplification of T cell responses. ..
- Sektioglu I, Carretero R, Bulbuc N, Bald T, TÃ¼ting T, Rudensky A, et al. Basophils Promote Tumor Rejection via Chemotaxis and Infiltration of CD8+ T Cells. Cancer Res. 2017;77:291-302 pubmed publisher..Intratumoral basophils enhanced CD8+ T-cell infiltration via production of chemokines CCL3 and CCL4; antibody-based blocking of these chemokines inhibited CD8+ T-cell infiltration...
- Scully P, MacSharry J, O Mahony D, Lyons A, O BRIEN F, Murphy S, et al. Bifidobacterium infantis suppression of Peyer's patch MIP-1? and MIP-1? secretion during Salmonella infection correlates with increased local CD4+CD25+ T cell numbers. Cell Immunol. 2013;281:134-40 pubmed publisher..This study suggests that although B. infantis 35624-induced Tregs correlate with inhibition of chemokine secretion within the mucosa of pathogen infected animals, indirect cellular mechanisms may play a role. ..
- Ji Y, Kim H, Bae K, Lee S, Kim M, Ryoo Z. Hepatic serum amyloid A1 aggravates T cell-mediated hepatitis by inducing chemokines via Toll-like receptor 2 in mice. J Biol Chem. 2015;290:12804-11 pubmed publisher..Hepatic Saa1 accelerated T cell-mediated hepatitis by inducing chemokine production and activating T cells by TLR2. Therefore, Saa1 might be a novel inflammatory factor that acts as a chemokine modulator in hepatitis. ..
- Sherry B, Tekamp Olson P, Gallegos C, Bauer D, Davatelis G, Wolpe S, et al. Resolution of the two components of macrophage inflammatory protein 1, and cloning and characterization of one of those components, macrophage inflammatory protein 1 beta. J Exp Med. 1988;168:2251-9 pubmed..9% sequence identity) products of different genes. ..
- Proffitt J, Crabtree G, Grove M, Daubersies P, Bailleul B, Wright E, et al. An ATF/CREB-binding site is essential for cell-specific and inducible transcription of the murine MIP-1 beta cytokine gene. Gene. 1995;152:173-9 pubmedThe murine macrophage inflammatory protein 1 beta mRNA (MIP-1 beta) is rapidly and transiently induced in macrophages by lipopolysaccharide (LPS), serum or cycloheximide...
- Pace L, Tempez A, Arnold Schrauf C, Lemaitre F, Bousso P, Fetler L, et al. Regulatory T cells increase the avidity of primary CD8+ T cell responses and promote memory. Science. 2012;338:532-6 pubmed publisher..These results suggest that T(regs) are important regulators of the homeostasis of CD8(+) T cell priming and play a critical role in the induction of high-avidity primary responses and effective memory. ..
- Grattan M, Mi Q, Meagher C, Delovitch T. Congenic mapping of the diabetogenic locus Idd4 to a 5.2-cM region of chromosome 11 in NOD mice: identification of two potential candidate subloci. Diabetes. 2002;51:215-23 pubmed..Three potential candidate genes, platelet activating factor acetylhydrolase Ib1, nitric oxide synthase-2, and CC chemokine genes, are localized in the 5.2-cM interval. ..
- Jaramillo M, Godbout M, Olivier M. Hemozoin induces macrophage chemokine expression through oxidative stress-dependent and -independent mechanisms. J Immunol. 2005;174:475-84 pubmed..falciparum HZ and synthetic HZ increase mRNA levels of various chemokine transcripts (MIP-1alpha/CCL3, MIP-1beta/CCL4, MIP-2/CXCL2, and MCP-1/CCL2) in murine B10R Mphi...
- Blackburn C, Griffith J, Morahan G. A high-resolution map of the chromosomal region surrounding the nude gene. Genomics. 1995;26:308-17 pubmed..We also report the typing of the above microsatellite markers in the AKXD, AKXL, BXD, CXB, and BXH recombinant inbred strains, which confirmed the relative order and separation of loci in this region. ..
- Oliveira S, Lira S, Martinez A C, Wiekowski M, Sullivan L, Lukacs N. Increased responsiveness of murine eosinophils to MIP-1beta (CCL4) and TCA-3 (CCL1) is mediated by their specific receptors, CCR5 and CCR8. J Leukoc Biol. 2002;71:1019-25 pubmed..calcium flux in antigen-elicited and peripheral blood eosinophils, and MCP-1 (CCL2), MDC (CCL22), MIP-1beta (CCL4), and TCA-3 (CCL1) did not...
- Chandrasekar B, Deobagkar Lele M, Victor E, Nandi D. Regulation of chemokines, CCL3 and CCL4, by interferon ? and nitric oxide synthase 2 in mouse macrophages and during Salmonella enterica serovar typhimurium infection. J Infect Dis. 2013;207:1556-68 pubmed publisher..In this study, the repression of CCL3 and CCL4 by IFN-? and nitric oxide synthase 2 (NOS2) in macrophages and upon Salmonella typhimurium infection of mice was ..
- Wilson S, Billings P, D EUSTACHIO P, Fournier R, Geissler E, Lalley P, et al. Clustering of cytokine genes on mouse chromosome 11. J Exp Med. 1990;171:1301-14 pubmed
- Nakajima T, Inagaki N, Tanaka H, Tanaka A, Yoshikawa M, Tamari M, et al. Marked increase in CC chemokine gene expression in both human and mouse mast cell transcriptomes following Fcepsilon receptor I cross-linking: an interspecies comparison. Blood. 2002;100:3861-8 pubmed..markedly increased, and I-309 (CCL1), macrophage inflammatory protein-1alpha (MIP-1alpha) (CCL3) and MIP-1beta (CCL4) were found among the 10 most increased human and mouse transcripts from approximately 12 000 genes (including some ..
- Hardbower D, Asim M, Luis P, Singh K, Barry D, Yang C, et al. Ornithine decarboxylase regulates M1 macrophage activation and mucosal inflammation via histone modifications. Proc Natl Acad Sci U S A. 2017;114:E751-E760 pubmed publisher..Thus, ODC in macrophages tempers antimicrobial, M1 macrophage responses during bacterial infections through histone modifications and altered euchromatin formation, leading to the persistence and pathogenesis of these organisms. ..
- Graber D, Costine B, Hickey W. Early inflammatory mediator gene expression in two models of traumatic brain injury: ex vivo cortical slice in mice and in vivo cortical impact in piglets. J Neuroinflammation. 2015;12:76 pubmed publisher..Interleukin-1Î² (IL-1Î²), tumor necrosis factor-Î± (TNF-Î±), chemokine ligands 2 (CCL2), 3 (CCL3), 4 (CCL4), and prostaglandin-endoperoxide synthase 2 (PTGS2) mRNAs increased within 5 h after injury in mouse cortical ..
- Krulova M, Havelková H, Kosarová M, Holan V, Hart A, Demant P, et al. IL-2-induced proliferative response is controlled by loci Cinda1 and Cinda2 on mouse chromosomes 11 and 12: a distinct control of the response induced by different IL-2 concentrations. Genomics. 1997;42:11-5 pubmed..Understanding the action of genetic factors, such as Cinda1 and Cinda2, that control T cell function is expected to contribute to the efficient analysis of the genetic control of susceptibility to infections and autoimmune diseases. ..
- Menten P, Saccani A, Dillen C, Wuyts A, Struyf S, Proost P, et al. Role of the autocrine chemokines MIP-1alpha and MIP-1beta in the metastatic behavior of murine T cell lymphoma. J Leukoc Biol. 2002;72:780-9 pubmed..This delicate balance should be considered in the design of antichemokine strategies in different tumor types. ..
- Roussoulières A, Raisky O, Chalabreysse L, Dureau G, Cerutti C, Thieblemont C, et al. Identification and characterization of two genes (MIP-1beta, VE-CADHERIN) implicated in acute rejection in human heart transplantation: use of murine models in tandem with cDNA arrays. Circulation. 2005;111:2636-44 pubmed..We have demonstrated that the upregulation of MIP-1beta and downregulation of VE-cadherin may strongly participate in human acute heart rejection. ..
- Horton M, Burdick M, Strieter R, Bao C, Noble P. Regulation of hyaluronan-induced chemokine gene expression by IL-10 and IFN-gamma in mouse macrophages. J Immunol. 1998;160:3023-30 pubmed..These data identify a previously unrecognized role for IL-10 and IFN-gamma as regulators of ECM-induced macrophage expression of inflammatory chemokines. ..
- Teuscher C, Butterfield R, Ma R, Zachary J, Doerge R, Blankenhorn E. Sequence polymorphisms in the chemokines Scya1 (TCA-3), Scya2 (monocyte chemoattractant protein (MCP)-1), and Scya12 (MCP-5) are candidates for eae7, a locus controlling susceptibility to monophasic remitting/nonrelapsing experimental allergic enceph. J Immunol. 1999;163:2262-6 pubmed..Similarly, cDNA sequence polymorphisms in Nos2, Scya3, Scya4, Scya5, Scya6, Scya7, Scya9, Scya10, and Scya11 were excluded as candidates for eae7...
- Saika F, Kiguchi N, Kobayashi Y, Fukazawa Y, Kishioka S. CC-chemokine ligand 4/macrophage inflammatory protein-1? participates in the induction of neuropathic pain after peripheral nerve injury. Eur J Pain. 2012;16:1271-80 pubmed publisher..Therefore, investigation of this cascade might be a validated approach for the elucidation of neuropathic pain mechanisms. ..
- de Valle E, Grigoriadis G, O Reilly L, Willis S, Maxwell M, Corcoran L, et al. NF?B1 is essential to prevent the development of multiorgan autoimmunity by limiting IL-6 production in follicular B cells. J Exp Med. 2016;213:621-41 pubmed publisher..Collectively, our findings identify a previously unrecognized role for NF?B1 in preventing multiorgan autoimmunity through its negative regulation of Il-6 gene expression in Fo B cells. ..
- Ishikawa K, Yoshida S, Nakao S, Sassa Y, Asato R, Kohno R, et al. Bone marrow-derived monocyte lineage cells recruited by MIP-1β promote physiological revascularization in mouse model of oxygen-induced retinopathy. Lab Invest. 2012;92:91-101 pubmed publisher..Overall, these findings indicate that the MIP-1β induction of BM-MLCs might possibly be used to promote intraretinal revascularization and thus prevent the abnormal NV in ischemic vision-threatening retinal diseases. ..
- Gewiese Rabsch J, Drucker C, Malchow S, Scheller J, Rose John S. Role of IL-6 trans-signaling in CCl?induced liver damage. Biochim Biophys Acta. 2010;1802:1054-61 pubmed publisher..We conclude that IL-6 trans-signaling via the soluble IL-6R is important for the physiologic response of the liver to CCl? induced chemical damage. ..