The role of PGE(2) in the differentiation of dendritic cells: how do dendritic cells influence T-cell polarization and chemokine receptor expression?

The role of prostaglandin E(2) (PGE(2)) in the function of dendritic cells (DCs), T-cell polarization, and expression of chemokine receptors was evaluated in human cells. Immature DCs were generated from peripheral blood CD14(+) cells using a combination of GM-CSF and interleukin-4 (IL-4) with or wi...

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Published in:Stem cells (Dayton, Ohio) Ohio), 2002, Vol.20 (5), p.448-459
Main Authors: Lee, Je-Jung, Takei, Masao, Hori, Shinichi, Inoue, Yoshiko, Harada, Yukie, Tanosaki, Ryuji, Kanda, Yoshinobu, Kami, Masayuki, Makimoto, Atsushi, Mineishi, Shin, Kawai, Hiroyuki, Shimosaka, Akihiro, Heike, Yuji, Ikarashi, Yoshinori, Wakasugi, Hiro, Takaue, Yoichi, Hwang, Tai-Ju, Kim, Hyeoung-Joon, Kakizoe, Tadao
Format: Article
Language:English
Subjects:
CD3 Complex - drug effects
CD3 Complex - immunology
Cell Culture Techniques
Cell Differentiation - drug effects
Cell Differentiation - immunology
Cell Polarity - drug effects
Cell Polarity - immunology
Cell Size - drug effects
Cell Size - immunology
Dendritic Cells - drug effects
Dendritic Cells - immunology
Dendritic Cells - metabolism
Dinoprostone - metabolism
Dinoprostone - pharmacology
Endocytosis - drug effects
Endocytosis - immunology
Granulocyte-Macrophage Colony-Stimulating Factor - pharmacology
Humans
Interferon-gamma - metabolism
Interferon-gamma - secretion
Interleukin-10 - metabolism
Interleukin-10 - secretion
Interleukin-12 - metabolism
Interleukin-12 - secretion
Interleukin-4 - pharmacology
Lymphocyte Activation - drug effects
Lymphocyte Activation - immunology
Phenotype
Receptors, CCR1
Receptors, Chemokine - drug effects
Receptors, Chemokine - immunology
T-Lymphocytes - drug effects
T-Lymphocytes - immunology
T-Lymphocytes - metabolism
Th1 Cells - drug effects
Th1 Cells - immunology
Th1 Cells - metabolism
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Summary:The role of prostaglandin E(2) (PGE(2)) in the function of dendritic cells (DCs), T-cell polarization, and expression of chemokine receptors was evaluated in human cells. Immature DCs were generated from peripheral blood CD14(+) cells using a combination of GM-CSF and interleukin-4 (IL-4) with or without PGE(2). On day 6, maturation of DCs was induced by the addition of tumor necrosis factor alpha with or without PGE(2). DCs harvested on day 6 (immature DCs) or day 9 (mature DCs) were examined using functional assays. In the presence of PGE(2), immature and mature DCs showed, phenotypically, a lower expression of CD1a and, functionally, a higher allostimulatory capacity at a high DC/T-cell ratio than control cells cultured in the absence of PGE(2). DCs cultured in the presence of PGE(2) induced the differentiation of naïve T cells toward a helper T-cell type 1 (Th1) response, which was independent of IL-12 secretion in the basal state despite a slightly lower interferon gamma secretion compared with control cells. However, the function of cytotoxicity-stimulating autologous T cells was not augmented by the addition of PGE(2). Immature DCs expressed the inflammatory chemokine receptors, CCR1 and CXCR4, but not CCR6, regardless of the presence or absence of PGE(2). Mature DCs expressed CCR7 equally, measured using a migration test and the measurement of calcium flux with macrophage inflammatory protein-3beta and reverse transcription-polymerase chain reaction assay in all of the groups. All of these findings suggest that PGE(2) affects the DC-promoted differentiation of naïve T cells to a Th1 response in the basal state, without affecting chemokine receptor expression on DCs.
ISSN:1066-5099
1549-4918
DOI:10.1634/stemcells.20-5-448