The Experts below are selected from a list of 132 Experts worldwide ranked by ideXlab platform

Jochen Ringe - One of the best experts on this subject based on the ideXlab platform.

  • mesenchymal stem cells and their chondrogenic differentiated and dedifferentiated progeny express Chemokine Receptor CCR9 and chemotactically migrate toward ccl25 or serum
    Stem Cell Research & Therapy, 2013
    Co-Authors: Mujib Ullah, Jan Eucker, Michael Sittinger, Jochen Ringe
    Abstract:

    Guided migration of chondrogenically differentiated cells has not been well studied, even though it may be critical for growth, repair, and regenerative processes. The Chemokine CCL25 is believed to play a critical role in the directional migration of leukocytes and stem cells. To investigate the motility effect of serum- or CCL25-mediated chemotaxis on chondrogenically differentiated cells, mesenchymal stem cells (MSCs) were induced to chondrogenic lineage cells. MSC-derived chondrogenically differentiated cells were characterized for morphology, histology, immunohistochemistry, quantitative polymerase chain reaction (qPCR), surface profile, and serum- or CCL25-mediated cell migration. Additionally, the Chemokine Receptor, CCR9, was examined in different states of MSCs. The chondrogenic differentiated state of MSCs was positive for collagen type II and Alcian blue staining, and showed significantly upregulated expression of COL2A1 and SOX9, and downregulated expression of CD44, CD73, CD90, CD105 and CD166, in contrast to the undifferentiated and dedifferentiated states of MSCs. For the chondrogenic differentiated, undifferentiated, and dedifferentiated states of MSCs, the serum-mediated chemotaxis was in a percentage ratio of 33%:84%:85%, and CCL25-mediated chemotaxis was in percentage ratio of 12%:14%:13%, respectively. On the protein level, CCR9, Receptor of CCL25, was expressed in the form of extracellular and intracellular domains. On the gene level, qPCR confirmed the expression of CCR9 in different states of MSCs. CCL25 is an effective cue to guide migration in a directional way. In CCL25-mediated chemotaxis, the cell-migration rate was almost the same for different states of MSCs. In serum-mediated chemotaxis, the cell-migration rate of chondrogenically differentiated cells was significantly lower than that in undifferentiated or dedifferentiated cells. Current knowledge of the surface CD profile and cell migration could be beneficial for regenerative cellular therapies.

  • Mesenchymal stem cells and their chondrogenic differentiated and dedifferentiated progeny express Chemokine Receptor CCR9 and chemotactically migrate toward CCL25 or serum.
    Stem cell research & therapy, 2013
    Co-Authors: Mujib Ullah, Jan Eucker, Michael Sittinger, Jochen Ringe
    Abstract:

    Introduction Guided migration of chondrogenically differentiated cells has not been well studied, even though it may be critical for growth, repair, and regenerative processes. The Chemokine CCL25 is believed to play a critical role in the directional migration of leukocytes and stem cells. To investigate the motility effect of serum- or CCL25-mediated chemotaxis on chondrogenically differentiated cells, mesenchymal stem cells (MSCs) were induced to chondrogenic lineage cells.

Mujib Ullah - One of the best experts on this subject based on the ideXlab platform.

  • mesenchymal stem cells and their chondrogenic differentiated and dedifferentiated progeny express Chemokine Receptor CCR9 and chemotactically migrate toward ccl25 or serum
    Stem Cell Research & Therapy, 2013
    Co-Authors: Mujib Ullah, Jan Eucker, Michael Sittinger, Jochen Ringe
    Abstract:

    Guided migration of chondrogenically differentiated cells has not been well studied, even though it may be critical for growth, repair, and regenerative processes. The Chemokine CCL25 is believed to play a critical role in the directional migration of leukocytes and stem cells. To investigate the motility effect of serum- or CCL25-mediated chemotaxis on chondrogenically differentiated cells, mesenchymal stem cells (MSCs) were induced to chondrogenic lineage cells. MSC-derived chondrogenically differentiated cells were characterized for morphology, histology, immunohistochemistry, quantitative polymerase chain reaction (qPCR), surface profile, and serum- or CCL25-mediated cell migration. Additionally, the Chemokine Receptor, CCR9, was examined in different states of MSCs. The chondrogenic differentiated state of MSCs was positive for collagen type II and Alcian blue staining, and showed significantly upregulated expression of COL2A1 and SOX9, and downregulated expression of CD44, CD73, CD90, CD105 and CD166, in contrast to the undifferentiated and dedifferentiated states of MSCs. For the chondrogenic differentiated, undifferentiated, and dedifferentiated states of MSCs, the serum-mediated chemotaxis was in a percentage ratio of 33%:84%:85%, and CCL25-mediated chemotaxis was in percentage ratio of 12%:14%:13%, respectively. On the protein level, CCR9, Receptor of CCL25, was expressed in the form of extracellular and intracellular domains. On the gene level, qPCR confirmed the expression of CCR9 in different states of MSCs. CCL25 is an effective cue to guide migration in a directional way. In CCL25-mediated chemotaxis, the cell-migration rate was almost the same for different states of MSCs. In serum-mediated chemotaxis, the cell-migration rate of chondrogenically differentiated cells was significantly lower than that in undifferentiated or dedifferentiated cells. Current knowledge of the surface CD profile and cell migration could be beneficial for regenerative cellular therapies.

  • Mesenchymal stem cells and their chondrogenic differentiated and dedifferentiated progeny express Chemokine Receptor CCR9 and chemotactically migrate toward CCL25 or serum.
    Stem cell research & therapy, 2013
    Co-Authors: Mujib Ullah, Jan Eucker, Michael Sittinger, Jochen Ringe
    Abstract:

    Introduction Guided migration of chondrogenically differentiated cells has not been well studied, even though it may be critical for growth, repair, and regenerative processes. The Chemokine CCL25 is believed to play a critical role in the directional migration of leukocytes and stem cells. To investigate the motility effect of serum- or CCL25-mediated chemotaxis on chondrogenically differentiated cells, mesenchymal stem cells (MSCs) were induced to chondrogenic lineage cells.

Joseph Kim - One of the best experts on this subject based on the ideXlab platform.

  • abstract 4009 ccl25 CCR9 axis mediates pancreatic cancer progression through beta catenin activation
    Cancer Research, 2013
    Co-Authors: Eileen L Heinrich, Wendy Lee, Carrie Luu, Joseph Kim
    Abstract:

    Proceedings: AACR 104th Annual Meeting 2013; Apr 6-10, 2013; Washington, DC Background: Expression of the Chemokine Receptor CCR9 is elevated in select solid organ cancers; and may contribute to drug resistance. However, there is no data for the role of CCR9 in GI cancers, aside from our prior work which demonstrated elevated expression in pancreatic cancer. Our current studies have uncovered activation of a novel CCR9-mediated molecular pathway and suggest that CCR9 may play a critical role in cancer progression through the aberrant activation of β-catenin. Methods: Immunohistochemistry and western blotting were used to assess CCR9 expression. We exposed human pancreatic cancer cell lines to CCL25 and evaluated levels of activated β-catenin and phosphorylated AKT via western blot. Proliferation and invasion were measured using an ATP-based assay and a Boyden chamber assay, respectively. IC50 of gemcitabine was determined using an acid phosphatase assay. Results: We have previously shown that CCR9 is expressed in human and murine PanIN lesions and in a human pancreatic cancer cell line. Here we expand upon these findings to show CCR9 expression in human pancreatic cancer tissue samples and in multiple cell lines. We determined that stimulation of CCR9 by its ligand, CCL25, signals through AKT and β-catenin to increase cell proliferation and invasion in pancreatic cancer cell lines. Following treatment with CCL25, cell proliferation was increased by an average of 20% across all cell lines (p<0.01). Pre-treatment with the PI3K inhibitor, LY294002, inhibited the CCL25-mediated increase in proliferation. We further show a CCL25-mediated increase in invasion. Using a modified Boyden chamber matrigel invasion assay, we determined that CCL25 as a chemoattractant heightened the invasive abilities of our pancreatic cancer cell lines by 3-fold. Inhibiting PI3K activation blocked this increase. In addition, exposure to CCL25 led to reduced gemcitabine sensitivity. Pre-treatment with CCL25 increased the IC50 of gemcitabine by 7-fold in PANC-1 cells, from 0.1μM to 0.77μM (p=0.005) and 5.5-fold in AsPC-1 cells from 17.7μM to 96.7μM (p=0.008), indicating a drastic decrease in the effectiveness of gemcitabine when CCL25 is present. Conclusions: The current paucity of effective therapies for pancreatic cancer presents a significant clinical challenge. This highlights the need to identify and study mechanisms and pathways involved in pancreatic cancer progression. Determining the role of CC9R in pancreatic cancer and targeting the CCL25-CCR9-β-catenin pathway may therefore present an innovative, clinically significant therapeutic target for pancreatic cancer. Citation Format: Eileen L. Heinrich, Jianming Lu, Wendy Lee, Carrie Luu, Joseph Kim. CCL25-CCR9 axis mediates pancreatic cancer progression through beta-catenin activation. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4009. doi:10.1158/1538-7445.AM2013-4009

  • Paracrine Activation of Chemokine Receptor CCR9 Enhances The Invasiveness of Pancreatic Cancer Cells
    Cancer microenvironment : official journal of the International Cancer Microenvironment Society, 2013
    Co-Authors: Eileen L Heinrich, Wendy Lee, Carrie Luu, Amanda K. Arrington, Joseph Kim
    Abstract:

    Chemokine Receptors mediate cancer progression and metastasis. We have previously examined Chemokine Receptor CCR9 expression in pancreatic cancer. Here, our objective was to evaluate pancreatic stellate cells (PSCs) as a source of CCL25, the CCR9 ligand, and as an activator of CCL25-CCR9 signaling in pancreatic cancer cells. CCL25 and CCR9 expression levels in human pancreatic cancer tissues and normal human pancreas were assessed by immunohistochemsitry. In vitro secretion of CCL25 in PSCs and PANC-1 cells was verified by enzyme-linked immunosorbent assay. Pancreatic cancer cell invasion was measured using a modified Boyden chamber assay with CCL25, PSC secreted proteins, and PANC-1 secreted proteins as the chemoattractant. There was immunostaining for CCR9 expression in human pancreatic tumor tissues, but not in normal pancreatic tissue. CCL25 expression was absent in the normal pancreatic tissue sample, but was observed in cancer cells and in the stromal cells surrounding the tumor. In vitro, both PANC-1 cells and PSCs secreted CCL25. In an invasion assay, exposure to CCL25, PSC- and PANC-1-conditioned media significantly increased the invasiveness of PANC-1 cells. Inclusion of a CCR9-neutralizing antibody in the invasion assay blocked the increase in invading cells elicited by the chemoattractants. Our studies show that pancreatic cancer invasiveness is enhanced by autocrine and paracrine stimulation of CCR9. PSCs in the tumor microenvironment appear to contribute to paracrine activation of CCR9. Investigations into CCR9 as a potential therapeutic target in pancreatic cancer must consider cancer cell autocrine signaling and also paracrine signaling from interactions in the tumor microenvironment.

Marc-andré Wurbel - One of the best experts on this subject based on the ideXlab platform.

  • 122 role of the cc Chemokine Receptor CCR9 in the regulation of inflammatory process during allergic airway inflammation
    World Allergy Organization Journal, 2012
    Co-Authors: Cynthia Lopezpacheco, Marc-andré Wurbel, Gisela Du Pont, Teresa I Fortoul, Gloria Soldevila, Eduardo A Garciazepeda
    Abstract:

    Background Airway eosinophilia and Th2 lymphocytes-recruitment to the lung are one of the main pathological features of asthma. It is clear now that the axis Chemokine/Chemokine Receptors have a role in controlling leukocyte recruitment and development of the inflammatory process observed in asthma. Although it has been reported that CCR9 Receptor is expressed in asthmatic patients, it is not known whether CCR9 may have a regulatory role of the development of this disease. Our aim was to analyze the expression of CCR9 in a murine model of allergic airway inflammation (WT) and compared to CCR9 deficient (KO) mice.

  • the Chemokine Receptor CCR9 is required for the t cell mediated regulation of chronic ileitis in mice
    Gastroenterology, 2011
    Co-Authors: Joshua D Wermers, Marc-andré Wurbel, Eoin N Mcnamee, Paul Jedlicka, Jesus Rivera Nieves
    Abstract:

    Background & Aims A balance between effector and regulatory T-cell (Treg) responses is required to maintain intestinal homeostasis. To regulate immunity, T cells migrate to the intestine using a combination of adhesion molecules and Chemokine Receptors. However, it is not known whether the migration pathways of effector cells and Tregs are distinct or shared. We sought to determine whether interaction between the Chemokine Receptor 9 (CCR9) and its ligand, Chemokine ligand 25 (CCL25), allows effectors or Tregs to localize to chronically inflamed small intestine. Methods By using a mouse model that develops Crohn's-like ileitis (tumor necrosis factor Δadenosine uracyl-rich element [TNFΔARE] mice) we examined the role of CCL25–CCR9 interactions for effector and Treg traffic using flow cytometry, quantitative reverse-transcription polymerase chain reaction, immunohistochemistry, immunoneutralization, and proliferation analyses. Results In TNFΔARE mice, expression of CCL25 and the frequency of CCR9-expressing lymphocytes increased during late-stage disease. In the absence of CCR9, TNFΔARE mice developed exacerbated disease, compared with their CCR9-sufficient counterparts, which coincided with a deficiency of CD4 + /CD25 + /forkhead box P3 + and CD8 + /CD103 + Tregs within the intestinal lamina propria and mesenteric lymph nodes. Furthermore, the CD8 + /CCR9 + subset decreased the proliferation of CD4 + T cells in vitro. Administration of a monoclonal antibody against CCR9 to TNFΔARE mice exacerbated ileitis in vivo, confirming the regulatory role of CD8 + /CCR9 + cells. Conclusions Signaling of the Chemokine CCL25 through its Receptor CCR9 induces Tregs to migrate to the intestine. These findings raise concerns about the development of reagents to disrupt this pathway for the treatment of patients with Crohn's disease.

  • Chemokine Receptor CCR9 Contributes to the Localization of Plasma Cells to the Small Intestine
    The Journal of experimental medicine, 2004
    Co-Authors: Oliver Pabst, Lars Ohl, Meike Wendland, Marc-andré Wurbel, Elisabeth Kremmer, Bernard Malissen, Reinhold Förster
    Abstract:

    Humoral immunity in the gut-associated lymphoid tissue is characterized by the production of immunoglobulin A (IgA) by antibody-secreting plasma cells (PCs) in the lamina propria. The Chemokine CCL25 is expressed by intestinal epithelial cells and is capable of inducing chemotaxis of IgA+ PCs in vitro. Using a newly generated monoclonal antibody against murine CCR9, we show that IgA+ PCs express high levels of CCR9 in the mesenteric lymph node (MLN) and Peyer's patches (PPs), but down-regulate CCR9 once they are located in the small intestine. In CCR9-deficient mice, IgA+ PCs are substantially reduced in number in the lamina propria of the small intestine. In adoptive transfer experiments, CCR9-deficient IgA+ PCs show reduced migration into the small intestine compared with wild-type controls. Furthermore, CCR9 mutants fail to mount a regular IgA response to an orally administered antigen, although the architecture and cell type composition of PPs and MLN are unaffected and are functional for the generation of IgA PCs. These findings provide profound in vivo evidence that CCL25/CCR9 guides PCs into the small intestine.

  • selective generation of gut tropic t cells in gut associated lymphoid tissue galt requirement for galt dendritic cells and adjuvant
    Journal of Experimental Medicine, 2003
    Co-Authors: Bengt Johanssonlindbom, Marcus Svensson, Marc-andré Wurbel, Bernard Malissen, Gabriel Marquez, William W Agace
    Abstract:

    In the current study, we address the underlying mechanism for the selective generation of gut-homing T cells in the gut-associated lymphoid tissues (GALT). We demonstrate that DCs in the GALT are unique in their capacity to establish T cell gut tropism but in vivo only confer this property to T cells in the presence of DC maturational stimuli, including toll-like Receptor-dependent and -independent adjuvants. Thus, DCs from mesenteric LNs (MLNs), but not from spleen, supported expression of the Chemokine Receptor CCR9 and integrin α4β7 by activated CD8+ T cells. While DCs were also required for an efficient down-regulation of CD62L, this function was not restricted to MLN DCs. In an adoptive CD8+ T cell transfer model, antigen-specific T cells entering the small intestinal epithelium were homogeneously CCR9+α4β7+CD62Llow, and this phenotype was only generated in GALT and in the presence of adjuvant. Consistent with the CCR9+ phenotype of the gut-homing T cells, CCR9 was found to play a critical role in the localization of T cells to the small intestinal epithelium. Together, these results demonstrate that GALT DCs and T cell expression of CCR9 play critical and integrated roles during T cell homing to the gut.

Michael Sittinger - One of the best experts on this subject based on the ideXlab platform.

  • mesenchymal stem cells and their chondrogenic differentiated and dedifferentiated progeny express Chemokine Receptor CCR9 and chemotactically migrate toward ccl25 or serum
    Stem Cell Research & Therapy, 2013
    Co-Authors: Mujib Ullah, Jan Eucker, Michael Sittinger, Jochen Ringe
    Abstract:

    Guided migration of chondrogenically differentiated cells has not been well studied, even though it may be critical for growth, repair, and regenerative processes. The Chemokine CCL25 is believed to play a critical role in the directional migration of leukocytes and stem cells. To investigate the motility effect of serum- or CCL25-mediated chemotaxis on chondrogenically differentiated cells, mesenchymal stem cells (MSCs) were induced to chondrogenic lineage cells. MSC-derived chondrogenically differentiated cells were characterized for morphology, histology, immunohistochemistry, quantitative polymerase chain reaction (qPCR), surface profile, and serum- or CCL25-mediated cell migration. Additionally, the Chemokine Receptor, CCR9, was examined in different states of MSCs. The chondrogenic differentiated state of MSCs was positive for collagen type II and Alcian blue staining, and showed significantly upregulated expression of COL2A1 and SOX9, and downregulated expression of CD44, CD73, CD90, CD105 and CD166, in contrast to the undifferentiated and dedifferentiated states of MSCs. For the chondrogenic differentiated, undifferentiated, and dedifferentiated states of MSCs, the serum-mediated chemotaxis was in a percentage ratio of 33%:84%:85%, and CCL25-mediated chemotaxis was in percentage ratio of 12%:14%:13%, respectively. On the protein level, CCR9, Receptor of CCL25, was expressed in the form of extracellular and intracellular domains. On the gene level, qPCR confirmed the expression of CCR9 in different states of MSCs. CCL25 is an effective cue to guide migration in a directional way. In CCL25-mediated chemotaxis, the cell-migration rate was almost the same for different states of MSCs. In serum-mediated chemotaxis, the cell-migration rate of chondrogenically differentiated cells was significantly lower than that in undifferentiated or dedifferentiated cells. Current knowledge of the surface CD profile and cell migration could be beneficial for regenerative cellular therapies.

  • Mesenchymal stem cells and their chondrogenic differentiated and dedifferentiated progeny express Chemokine Receptor CCR9 and chemotactically migrate toward CCL25 or serum.
    Stem cell research & therapy, 2013
    Co-Authors: Mujib Ullah, Jan Eucker, Michael Sittinger, Jochen Ringe
    Abstract:

    Introduction Guided migration of chondrogenically differentiated cells has not been well studied, even though it may be critical for growth, repair, and regenerative processes. The Chemokine CCL25 is believed to play a critical role in the directional migration of leukocytes and stem cells. To investigate the motility effect of serum- or CCL25-mediated chemotaxis on chondrogenically differentiated cells, mesenchymal stem cells (MSCs) were induced to chondrogenic lineage cells.