Disease relevance of Ccl5

• Recently, it has been shown that genetic polymorphisms can result in diminished expression of CCL5, which results in increased susceptibility to and progression of infectious diseases [1].
• To determine the contribution of CCL5 to pneumococcal surface antigen A-specific humoral and cellular pneumococcal immunity, mice were treated with anti-CCL5 or control Abs before and during Streptococcus pneumoniae strain EF3030-challenge for the initiation of carriage [1].
• Although RANTES expression was observed during the entire course of disease, anti-RANTES treatment had no effect on clinical disease progression [2].
• Contrasting roles for RANTES and macrophage inflammatory protein-1 alpha (MIP-1 alpha) in a murine model of allergic peritonitis [3].
• These findings led us to use Met-RANTES, a selective CCR1 and CCR5 antagonist, to modulate the acute T cruzi-elicited myocarditis [4].

High impact information on Ccl5

• The protective effect of Ccl5 requires activation of the Ccr5 chemokine receptor and consequent bilateral activation of G(alphai)-PI3K-AKT and G(alphai)-MEK-ERK signaling pathways [5].
• Virus-inducible levels of Ccl5 are required to prevent apoptosis of virus-infected mouse macrophages in vivo and mouse and human macrophages ex vivo [5].
• RANTES production by memory phenotype T cells is controlled by a posttranscriptional, TCR-dependent process [6].
• An examination of differences in gene expression between memory and naive phenotype T cells revealed elevated levels of mRNA for several chemokines, especially RANTES, in memory phenotype T cells [6].
• In vivo, CD8+ memory T cells proliferate continuously and slowly in response to IL-15; however, IL-15 does not stimulate RANTES secretion [6].

Chemical compound and disease context of Ccl5

• The investigation examined MuRantes expression in primary embryonic fibroblasts and fresh peritoneal macrophages after Newcastle disease virus induction and whole organs after lipopolysaccharide induction [7].
• In addition, chemokines previously associated with allergen-induced pulmonary disease, CCL2, CCL5, and CCL6, were significantly reduced in the lungs of the imatinib-treated animals [8].
• TARC and RANTES, but not CTACK, are induced in two models of allergic contact dermatitis. Effects of cilomilast and diflorasone diacetate on T-cell-attracting chemokines [9].
• However, RANTES, MCP-1, MIP 1-beta, and TRANCE given together with a DNA vaccine expressing a truncated and thus secreted version of the rabies virus glycoprotein enhanced the response suggesting that the tested genetic adjuvants promoted preferentially presentation of reprocessed antigen originating from transduced tissue cells [10].
• Steroid treatment instituted post-challenge selectively inhibited the CC-chemokine regulation upon activation, normal T cell expressed and secrted (RANTES), permitted continued egression of eosinophils into airway lumen, and resolved the tissue eosinophilia [11].

Biological context of Ccl5

• Serial Analysis of Gene Expression in Progressing and Regressing Mouse Tumors Implicates the Involvement of RANTES and TARC in Antitumor Immune Responses [12].
• In contrast, mutation of the other two putative NF-kappaB binding sites did not affect RANTES promoter activity significantly [13].
• In vitro chemotaxis assays confirmed that lung lavage fluid from MHV-68-infected mice had chemotactic activity, which was partially blocked by antibodies to IP-10 and RANTES [14].
• Airway eosinophilia, OVA-specific IgE in serum, and chemokine eotaxin and RANTES (regulated upon activation, normal T cell expressed and secreted) in bronchoalveolar lavage fluid were measured by lung histology, Diff-Quick staining, and ELISA [15].
• The protein-coding region of this cDNA is 73, 71, 50, and 48% identical in nucleic acid sequence to those of human macrophage chemoattractant protein (MCP) 3, MCP-1, macrophage inflammatory protein (MIP) 1 alpha, and RANTES, respectively [16].

Anatomical context of Ccl5

• CCL5 blockade resulted in a decrease of CD4(+) and CD8(+) T cells as well as CD11b(+) cells in the spleen, cervical lymph node, lung, and nasopharyngeal associated lymphoid tissue during the recognition phase of the pneumococcal adaptive immune response [1].
• Chemokine induction was also observed after treatment of splenic DC and neonatal microglia with RANTES, but not after treatment of thymocytes or splenocytes depleted of adherent cells [17].
• RANTES-induced chemokine cascade in dendritic cells [17].
• MCP-1 and RANTES expression was also seen in tubular epithelial cells [18].
• Leukocyte recruitment and viral replication in influenza-infected RANTES knockout(-/-) mice were similar to that in control mice, showing that RANTES is not essential for the immune response to influenza infection [19].

Associations of Ccl5 with chemical compounds

• Here we report that RANTES expression in IRF-8-null macrophages stimulated with interferon-gamma and lipopolysaccharide is markedly decreased [20].
• However, at d 3 after infection, male vitamin C-deficient mice had less expression of mRNA for RANTES, monocyte chemotactic protein-1 (MCP-1), and IL-12 compared with male controls [21].
• RANTES is a member of the C-C subfamily of chemokines that functions as a proinflammatory chemoattractant for CD4+ T cells, monocytes, and eosinophils, and as an activator of basophils to release histamine [22].
• RANTES (CCL5) regulates airway responsiveness after repeated allergen challenge [23].
• Sixty days after transplantation, intra-allograft expression of chemokines in hearts from gallium nitrate-treated recipients indicated low levels of MIP-1alpha, MIP-1beta, and KC but high levels of interferon-gamma-inducible protein and RANTES [24].

Enzymatic interactions of Ccl5

• Finally, RANTES treatment induces nuclear translocation of phosphorylated RSK in astrocytes [25].

Co-localisations of Ccl5

• In the allograft, the chemokine also colocalizes with CD4+ T cells that do not produce RANTES [26].

Regulatory relationships of Ccl5

• This study uncovers a novel IFNgamma-induced pathway in RANTES expression mediated by IRF-1 in macrophages and elucidates an important host defense mechanism against neoplastic transformation [27].
• Adenovirus-mediated gene transduction of IRF-1 in primary macrophages resulted in enhanced RANTES expression [27].
• IRF-8 can activate RANTES gene transcription in synergism with IRF-1 [20].
• Treatment with RANTES specifically modulated astrocyte receptors upregulating intercellular adhesion molecule 1 (ICAM-1) and downregulating CX3CR1 expression [28].
• Intrarenal CCL5 production was enhanced by Flt3L administration, in association with marked increases in interstitial CD45+ mononuclear cells [29].

Other interactions of Ccl5

• RANTES-mediated chemokine amplification in DC may prolong inflammatory responses and shape the microenvironment, potentially enhancing acquired and innate immune responses [17].
• TNF-alpha-treated DC lose responsiveness to RANTES [17].
• Interferon regulatory factor 1 is an essential and direct transcriptional activator for interferon {gamma}-induced RANTES/CCl5 expression in macrophages [27].
• After initiating GN, MCP-1 and RANTES and their receptors are readily downregulated [30].
• TNFR1-/- mice with EAE had significantly higher expression of CXCL10 mRNA (but not CCL5 mRNA) in the CNS compared to WT mice with EAE [31].

Analytical, diagnostic and therapeutic context of Ccl5

• The expression of the beta-chemokine MIP-1alpha, MIP-1beta, RANTES, and JE proteins by murine macrophages cultured with trypomastigote forms of T. cruzi was confirmed by immunocytochemistry [32].
• Isograft expression of RANTES and IP-10 was undetectable at the late time points [33].
• The expression of macrophage inflammatory protein (MIP)-1alpha, MIP-1beta, and regulated upon activation, normal T cell expressed and secreted (RANTES) was at low or undetectable levels at day 3 after transplantation but at high levels by day 8 after transplantation [24].
• In situ hybridization demonstrated that during the peak of inflammation, RANTES gene expression was localized to sites of inflammatory cell infiltration and P. carinii infection [34].
• The MuRantes protein could be detected in cell lysates of MCT epithelium by western blotting and in the cytoplasm of MCT cells by immunofluorescence using a polyclonal antibody generated against HuRantes fusion protein [35].

References