Disease relevance of Ccl6

• Immunoneutralization of peritoneal C10 levels with polyclonal anti-C10 antiserum during CLP-induced peritonitis negatively impacted mouse survival over 4 days [1].
• The lack of bacteremia in C10-treated mice appeared to be related, in part, to in vitro evidence that C10 significantly enhanced the bacterial phagocytic activity of peritoneal macrophages [1].
• Immunomodulatory role of C10 chemokine in a murine model of allergic bronchopulmonary aspergillosis [2].
• Hyperthermic stress (43 degrees C, 180 min), which induces reactivation of latent HSV-1 from TG cell cultures, significantly reduced IL-6 and C-10 levels from both uninfected and latently infected TG cell cultures [3].
• To explore the protective function of the mouse mrp1 protein during drug treatment, we investigated the toxicity caused by the anticancer drug etoposide-phosphate (ETOPOPHOS) in mice lacking the mrp1 gene (mrp1(-/-) mice) [4].

High impact information on Ccl6

• At the mechanistic level, bacterial levels in Stat6-/- mice were much lower than in WT mice, which was associated with increased peritoneal levels of interleukin (IL)-12, tumor necrosis factor (TNF)-alpha, macrophage-derived chemokine (MDC), and C10, known to enhance bacterial clearance [5].
• We show here that the lack of mrp1 protein results in increased etoposide-induced damage to the mucosa of the oropharyngeal cavity and to the seminiferous tubules of the testis [4].
• Our results indicate that specific inhibitors of MRP1 used to reverse MDR, in combination with carcinostatic drugs transported by MRP1, might lead to drug-induced mucositis, (temporary) infertility, and diabetes insipidus [4].
• We also find drug-induced polyuria in mrp1(-/-) mice, which correlates with the presence of mrp1 protein in the urinary collecting tubules, the major site of kidney water reabsorption [4].
• The high concentrations of mrp1 that we find in the basal layers of the oropharyngeal mucosa and in the basal membrane of the Sertoli cells in the testis apparently protect wild-type mice against this tissue damage [4].

Chemical compound and disease context of Ccl6

• One of these GP50/55-specific mAbs (C10) crossreacts with a 28-kD antigen (p28) expressed on the membrane of greater than 85% of activated mouse T and B lymphocytes, after in vitro activation with concanavalin A, Salmonella typhosa lipopolysaccharide, phorbol dibutyrate ester, or antigen, and on several murine T and B lymphocyte cell lines [6].
• Bilirubin protects astrocytes from its own toxicity by inducing up-regulation and translocation of multidrug resistance-associated protein 1 (Mrp1) [7].
• In this study, by using K-1735 melanoma system, we demonstrated that highly metastatic C4, M2, and X21 tumor cells express elevated MMP-2 mRNA and enzymatic activity, whereas poorly metastatic C10, C19, and C23 tumor cells express much lower levels [8].
• The effects of four monoesters of sucrose with different acyl chain lengths (palmitate, C16; myristate, C14; laurate, C12; and caprate, C10) on the aggregation state of amphotericin B (AmB), its binding to cholesterol and ergosterol, its toxicity to cells, and its lethality to mice were determined [9].
• A homogeneous, 140 Kd egg glycoprotein, SJe; 140-GP was nearly as effective as intact eggs in sensitizing for egg-focused pulmonary granuloma formation, while SEA, or the heterogeneous immunoaffinity (IA)-purified C10 antigens were ineffective [10].

Biological context of Ccl6

• CCL2 and CCL6 were localized to both monocular cells and muscle fibers, suggesting that dystrophic muscle may contribute toward chemotaxis [11].
• In contrast to this genomic structure, the C10 gene has four exons, with a novel second exon of 48 nucleotides [12].
• The gene for C10, a member of the beta-chemokine family, is located on mouse chromosome 11 and contains a novel second exon not found in other chemokines [12].
• Using a nontransformed alveolar type II epithelial cell line (C10), we show that alpha-quartz silica causes persistent dose-related increases in phosphorylation of c-Jun-NH2-terminal amino kinases (JNKs) that are inhibited by antioxidants (P < or = 0.05) [13].
• Alkylation of aminopterin (methotrexate) or carbon for nitrogen substitution (10-deazaaminopterin) at N-10 increased Km 3- to 6-fold, while alkylation at C10 (10-ethyl-10-deazaaminopterin) restored Km to near equivalency with aminopterin [14].

Anatomical context of Ccl6

• Although interleukin (IL)-13, a Th2 cytokine, has been shown to have direct effects on fibroblasts that support fibroproliferation, it is also a potent inducer of a novel CC chemokine, C10, which is chemotactic for mononuclear phagocytes [15].
• Recombinant rat CCL6 mediated the migration of microglia and astrocytes in vitro [16].
• These findings suggest that CCL6 may be a mediator released by microglia for cell-cell communication under physiological as well as pathological conditions of CNS [16].
• Finally the GM-CSF-mediated induction of C10 in peritoneal macrophages was eliminated when these cells presented antigen to established T cells of Th(1)phenotype [17].
• In situ hybridization and immunohistochemistry revealed expression of C10 in macrophages of the clot and the granulation tissue as well as in keratinocytes of the epidermis and the hair follicles at the wound edge [18].

Associations of Ccl6 with chemical compounds

• Macrophage inflammatory protein related protein-2 (mMRP-2) and Mu C10 (mMRP-1), which are murine C6 beta-chemokines, also inhibited colony formation by CB CD34+ cells [19].
• Thus, although the C10 gene contains a novel exon not found in any other members of the chemokine superfamily, its chromosomal location and conservation of cysteine residues and other structural features suggest that it evolved from the same ancestral gene as other members of the beta-chemokine family [12].
• By contrast, annexin 1 secretion is not blocked by other inhibitors of MRP1 (indomethacin, MK571), MRP2 (ochratoxin A1 or MK571), MRP5 (trequinsin or sulfinpyrazone) or by verapamil, cyclosporin A or glyburide [20].
• Most importantly, when EL4 cells were incubated in the presence of the MRP1 inhibitors indomethacin and MK 571 for 6 days, they started to express CD4 and CD8 molecules on their surface, producing double-positive cells and CD8 single-positive cells [21].
• In the harvested cells the transcripts for mdr1a and mrp1, but not those for mdr1b, mrp2 and CYP3A, were detected, and treatment with verapamil or rifampicin did not modify the levels of the transcripts [22].

Regulatory relationships of Ccl6

• Additionally, in C10 cells expressing a mutant form of TNF-R1, H2O2-induced JNK activation was also inhibited [23].

Other interactions of Ccl6

• The inhibition of C10 production by interferon gamma was not NO dependent [17].
• Using Northern blotting, RNase protection assay and Western blotting, we confirmed the injury-induced expression of C10 at the mRNA and protein level [18].
• No expression of C10 or MIP-2 was detected [24].
• Protein and messenger RNA (mRNA) levels of CC chemokines (monocyte/lymphocyte attractants), especially monocyte chemoattractant protein (MCP)-1, macrophage inflammatory protein (MIP)-1alpha, RANTES (regulated upon activation normal T-cell expressed and secreted), and C10, were preferentially induced in the lung by day 7 postallogeneic BMT [25].
• Among this family, C10 shows the highest homology to CCF18, and MIP-1 alpha also has a significant homology but to a lesser extent [26].

Analytical, diagnostic and therapeutic context of Ccl6

• At 24 h after CLP surgery, only 25% of C10-treated mice were bacteremic versus 85% of the control group that exhibited dissemination of bacteria into the circulation [1].
• The present study addressed the role of C10 in a murine model of septic peritonitis, induced by cecal ligation and puncture (CLP) [1].
• The intratracheal delivery of Asperigillus fumigatus Ag into A. fumigatus-sensitized mice resulted in significantly increased levels of C10 within the bronchoalveolar lavage, and these levels peaked at 48 h after A. fumigatus challenge [2].
• Intraperitoneal injection of thioglycollate increased peritoneal CCL6, which peaked at 4 h and remained elevated at 48 h [27].
• The CSF concentration of estradiol-17beta-glucuronide (E(2)17betaG) and 2,4-dinitrophenyl-S-glutathione (DNP-SG) in the CSF after intracerebroventricular and intravenous injection were compared between wild-type and Mrp1 gene knockout mice [28].

References