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C-C Motif (c-c + motif)
Selected AbstractsTumor-stromal crosstalk in invasion of oral squamous cell carcinoma: a pivotal role of CCL7INTERNATIONAL JOURNAL OF CANCER, Issue 2 2010Da-Woon Jung Abstract Recent studies have shown that stromal fibroblasts have a more profound influence on the initiation and progression of carcinoma than was previously appreciated. This study aimed at investigating the reciprocal relationship between cancer cells and their associated fibroblasts at both the molecular and cellular level in oral squamous cell carcinoma (OSCC). To identify key molecular regulators expressed by carcinoma-associated fibroblasts (CAF) that promote cancer cell invasion, microarrays were performed by comparing cocultured OSCC cells and CAF with monoculture controls. Microarray and real-time PCR analysis identified marked upregulation of the chemokine (C-C motif) ligand 7 (CCL7) in cocultured CAF. ELISA showed an elevated level of CCL7 secretion from CAF stimulated by coculture with OSCC cells. CCL7 promoted the invasion and migration of OSCC cells, and the invasiveness was inhibited by treatment with CCL7 neutralizing antibody. OSCC cells were shown to express CCR1, CCR2 and CCR3, receptors for CCL7, by RT-PCR. In addition, treatment with anti-CCR1 or anti-CCR3 antibody inhibited CCL7-induced OSCC cell migration, implicating that CCL7 promotes cancer cell migration through CCR1 and CCR3 on OSCC cells. Cytokine antibody array analysis of the supernatant from OSCC cell culture revealed that interleukin-1, was an inducer of CCL7 secretion by CAF. This study confirms the reciprocal relationship of the molecular crosstalk regulating the invasion of OSCC and describes new potential targets for future therapy. [source] Murine and human Langerhans cells express a functional histamine H4 receptor: modulation of cell migration and functionALLERGY, Issue 7 2010M. Gschwandtner To cite this article: Gschwandtner M, Rossbach K, Dijkstra D, Bäumer W, Kietzmann M, Stark H, Werfel T, Gutzmer R. Murine and human Langerhans cells express a functional histamine H4 receptor: modulation of cell migration and function. Allergy 2010; 65: 840,849. Abstract Background:, Histamine is an important mediator of allergic reactions, and recent studies indicated that the function of different types of antigen presenting cells (APC) can be modulated by histamine, in particular via the newly described histamine H4 receptor (H4R). Therefore, we investigated possible interactions of histamine via the H4R on Langerhans cells (LC), which represent the professional APC in the skin and therefore have an important role in the initiation and maintenance of allergic skin diseases. Methods:, The expression of the H4R was evaluated by real-time PCR, flow cytometry and immunofluorescence staining. The function of the H4R was determined by intracellular flow cytometric measurement of chemokine production and LC migration assays. Results:, Here, we show H4R expression on in vitro generated monocyte-derived LC (mRNA and protein) and on primary LC from murine and human skin samples (protein). The immunofluorescence staining in murine and human skin samples clearly proved that LC express the H4R in situ. Stimulation with histamine or a H4R agonist downregulated the chemokine (C-C motif) ligand 2 (CCL2) in human monocyte-derived LC and primary LC. Prestimulation with a selective H4R antagonist abolished this effect. Moreover, migration of LC from the epidermis was increased after H4R agonist stimulation in ex vivo migration assays using human epidermis and murine in vivo assays. Conclusion:, Our findings show that LC express a functional H4R and point towards a possible pathogenic relevance of the H4R in inflammatory and allergic diseases. [source] Lack of association between chemokine (C-C motif) receptor 3 (CCR3) gene and schizophrenia in the Korean populationPSYCHIATRY AND CLINICAL NEUROSCIENCES, Issue 5 2010Su Kang Kim MSc No abstract is available for this article. [source] Tissue expression of IL16 in prostate cancer and its association with recurrence after radical prostatectomy,THE PROSTATE, Issue 15 2010Eva Compérat Abstract BACKGROUND Genetic polymorphism located within the IL16 gene has been reported to be associated with aggressive prostate cancer (PCa). Our aim was to establish whether the tissue expression of IL16 is a prognostic factor of survival in PCa. METHODS The files of patients who underwent radical prostatectomy (RP) between 1995 and 2001 were reviewed. The cases were selected and classified according to the D'Amico classification for risk of recurrence (intermediate or high). The value of IL16 and its receptor CCR5 (chemokine (C-C motif) receptor 5) expression levels were determined as witness of aggressiveness patterns and markers of biological relapse in patients with PCa treated by RP. A tissue microarray of 304 cases was constructed. IL16 and CCR5 expression levels were characterized by immunohistochemistry. RESULTS IL16 expression was correlated with high Gleason score (i.e., >7) (P,<,0.01). It was not significant for CCR5. IL16 and CCR5 were not associated with prostate-specific antigen (PSA) or capsular extension of the disease. The accurate prediction of disease outcome, using stratification of cases, according to negative margins and D'Amico classification was significantly enhanced by status of IL16 expression (P,,,0.01). In univariate analyses, Gleason score, PSA level, stage and loss of IL16 expression were related to better biological-free survival (P,<,0.05) but not CCR5. In a multivariate analysis, IL16 expression, Gleason score, and tumor stage were independent factors for biochemical-free survival (P,=,0.001). CONCLUSIONS IL16 appears to be a useful prognostic factor in PCa. Its expression in PCa tissue was correlated to tumor aggressiveness and biochemical relapse of the disease. Prostate 70: 1622,1627, 2010. © 2010 Wiley-Liss, Inc. [source] Common promoter deletion is associated with 3.9-fold differential transcription of ovine CCR5 and reduced proviral level of ovine progressive pneumonia virusANIMAL GENETICS, Issue 5 2009S. N. White Summary Chemokine (C-C motif) Receptor 5 (CCR5) is a chemokine receptor that regulates immune cell recruitment in inflammation and serves as a coreceptor for human immunodeficiency virus (HIV). A human CCR5 coding deletion (termed delta-32) results in strong resistance to HIV infection, and sequence variants in CCR5 regulatory regions have been implicated in delayed progression to acquired immune deficiency syndrome. Both ovine progressive pneumonia virus (OPPV), also known as maedi-visna, and HIV are macrophage-tropic lentiviruses, have similar genomic structures, and cause lifelong persistent host infection, suggesting CCR5 may have a role in regulating OPPV provirus levels. Therefore, the ovine CCR5 genomic sequence was determined, and sequence variants were obtained from the open reading frame and surrounding regulatory sites. One CCR5 variant contained a 4-base deletion within a binding site for octamer transcription factors in the promoter region. A test for differential transcription from each allele in heterozygous animals showed a 3.9-fold transcription difference (P < 0.0001). OPPV proviral levels were also measured in 351 naturally exposed Rambouillet, Polypay and Columbia sheep. Deletion homozygotes showed reduced OPPV proviral levels among these animals (P < 0.01). The association of this CCR5 promoter deletion with OPPV levels will need to be validated in additional populations before the deletion can be recommended for widespread use in marker-assisted selection. However, because of the large impact on transcription and because CCR5 has roles in inflammation, recruitment of effector cells, and cell-mediated immunity, this deletion may play a role in the control of infections of many diverse pathogens of sheep. [source] The protein kinase C agonist PEP005 increases NF-,B expression, induces differentiation and increases constitutive chemokine release by primary acute myeloid leukaemia cellsBRITISH JOURNAL OF HAEMATOLOGY, Issue 6 2009Astrid Marta Olsnes Summary Acute myeloid leukaemia (AML) cells show constitutive release of several chemokines that occurs in three major clusters: (I) chemokine (C-C motif) ligand (CCL)2,4/chemokine (C-X-C motif) ligand (CXCL)1/8, (II) CCL5/CXCL9,11 and (III) CCL13/17/22/24/CXCL5. Ingenol-3-angelate (PEP005) is an activator of protein kinase C and has antileukaemic and immunostimulatory effects in AML. We investigated primary AML cells derived from 35 unselected patients and determined that PEP005 caused a dose-dependent increase in the release of chemokines from clusters I and II, including several T cell chemotactic chemokines. The release of granulocyte-macrophage colony-stimulating factor and hepatocyte growth factor was also increased. CCL2,4/CXCL1/8 release correlated with nuclear factor (NF)-,B expression in untreated AML cells, and PEP005-induced chemokine production was associated with further increases in the expression of the NF-,B subunits p50, p52 and p65. Increased DNA binding of NF-,B was observed during exposure to PEP005, and the specific NF-,B inhibitor BMS-345541 reduced constitutive chemokine release even in the presence of PEP005. Finally, PEP005 decreased expression of stem cell markers (CD117, CXCR4) and increased lineage-associated CD11b and CD14 expression. To conclude, PEP005 has a unique functional pharmacological profile in human AML. Previous studies have described proapoptotic and T cell stimulatory effects and the present study describes additional T cell chemotactic and differentiation-inducing effects. [source] | ||||||||||