| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
National Research Laboratory of DNA Medicine, Division of Molecular and Life Sciences, Pohang University of Science and Technology, Pohang, Korea
Phosphorothioate cytosine-guanine oligodeoxynucleotides (CpG
PS-ODNs) has been reported to induce Th1 immune responses against
coadministered Ags more efficiently than phosphodiester CpG ODNs (CpG
PO-ODNs). Here, we demonstrated that PS-ODNs, but not PO-ODNs, have a
chemotactic effect on primary macrophages, which is independent of the
CpG motif. In addition, the conjugation of a hexameric dG run
(dG6 run) at the 3' terminus reduced the concentration
required for the optimal chemotactic activity of PS-ODNs by 
10-fold.
Endosomal maturation blockers, such as monensin and chloroquine,
inhibited the chemotactic effect of PS-ODNs. The inhibition of the
activities of p38 mitogen-activated protein (MAP) kinase, and
extracellular signal-related kinases (ERKs) as well as phosphoinositide
3-kinase with their specific inhibitors also resulted in suppressing
the chemotaxis of primary macrophages induced by PS-ODNs. These results
indicate that the PS-ODN-mediated chemotaxis requires the activation of
ERKs, p38 MAP kinase, and phosphoinositide 3-kinase as well as
endosomal maturation. In addition, the phosphorylations of the p38 MAP
kinase, ERKs, and protein kinase B, Akt, were induced by PS-ODN, which
were further enhanced by the presence of both a dG6 run and
CpG motifs. Our findings suggest that the chemotactic activity of
PS-ODNs may be one of the mechanisms by which PS-ODNs exhibit stronger
immunomodulatory activities than PO-ODNs in
vivo.
This article has been cited by other articles:
|
|
 |
|
  K. Schroder, M. Lichtinger, K. M. Irvine, K. Brion, A. Trieu, I. L. Ross, T. Ravasi, K. J. Stacey, M. Rehli, D. A. Hume, et al. PU.1 and ICSBP control constitutive and IFN-{gamma}-regulated Tlr9 gene expression in mouse macrophages J. Leukoc. Biol., June 1, 2007; 81(6): 1577 - 1590. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. S. Spinner, R. B. Kascsak, G. LaFauci, H. C. Meeker, X. Ye, M. J. Flory, J. I. Kim, G. B. Schuller-Levis, W. R. Levis, T. Wisniewski, et al. CpG oligodeoxynucleotide-enhanced humoral immune response and production of antibodies to prion protein PrPSc in mice immunized with 139A scrapie-associated fibrils J. Leukoc. Biol., June 1, 2007; 81(6): 1374 - 1385. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. P. Sester, K. Brion, A. Trieu, H. S. Goodridge, T. L. Roberts, J. Dunn, D. A. Hume, K. J. Stacey, and M. J. Sweet CpG DNA Activates Survival in Murine Macrophages through TLR9 and the Phosphatidylinositol 3-Kinase-Akt Pathway J. Immunol., October 1, 2006; 177(7): 4473 - 4480. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. A. Sanjuan, N. Rao, K.-T. A. Lai, Y. Gu, S. Sun, A. Fuchs, W.-P. Fung-Leung, M. Colonna, and L. Karlsson CpG-induced tyrosine phosphorylation occurs via a TLR9-independent mechanism and is required for cytokine secretion. J. Cell Biol., March 27, 2006; 172(7): 1057 - 1068. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. K. Yoo, H. Kwon, L.-Y. Khil, L. Zhang, H.-S. Jun, and J.-W. Yoon IL-18 Induces Monocyte Chemotactic Protein-1 Production in Macrophages through the Phosphatidylinositol 3-Kinase/Akt and MEK/ERK1/2 Pathways J. Immunol., December 15, 2005; 175(12): 8280 - 8286. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. L. Roberts, J. A. Dunn, T. D. Terry, M. P. Jennings, D. A. Hume, M. J. Sweet, and K. J. Stacey Differences in Macrophage Activation by Bacterial DNA and CpG-Containing Oligonucleotides J. Immunol., September 15, 2005; 175(6): 3569 - 3576. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Wang, R. Alvarez, G. Roderiquez, E. Guan, Q. Caldwell, J. Wang, M. Phelan, and M. A. Norcross CpG-Independent Synergistic Induction of {beta}-Chemokines and a Dendritic Cell Phenotype by Orthophosphorothioate Oligodeoxynucleotides and Granulocyte-Macrophage Colony-Stimulating Factor in Elutriated Human Primary Monocytes J. Immunol., May 15, 2005; 174(10): 6113 - 6121. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. L. Roberts, M. J. Sweet, D. A. Hume, and K. J. Stacey Cutting Edge: Species-Specific TLR9-Mediated Recognition of CpG and Non-CpG Phosphorothioate-Modified Oligonucleotides J. Immunol., January 15, 2005; 174(2): 605 - 608. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Kwang Yoo, J. Ho Cho, S. Woo Lee, and Y. Chul Sung IL-12 Provides Proliferation and Survival Signals to Murine CD4+ T Cells Through Phosphatidylinositol 3-Kinase/Akt Signaling Pathway J. Immunol., October 1, 2002; 169(7): 3637 - 3643. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
