| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
*
Thomas E. Starzl Transplantation Institute and Department of Surgery, and Department of Molecular Genetics and Biochemistry, University of Pittsburgh, Pittsburgh, PA 15213;
Institute of Clinical Immunology and Transfusion Medicine, Justus-Liebig University of Giessen, Giessen, Germany;
Department of Dermatology and the University of Pittsburgh Cancer Institute, and
Department of Cell Biology and Physiology, Center for Biological Imaging, University of Pittsburgh, Pittsburgh, PA 15261
Aspirin is the most commonly used analgesic and antiinflammatory
agent. In this study, at physiological concentrations, it profoundly
inhibited CD40, CD80, CD86, and MHC class II expression on murine,
GM-CSF + IL-4 stimulated, bone marrow-derived myeloid dendritic cells
(DC). CD11c and MHC class I expression were unaffected. The inhibitory
action was dose dependent and was evident at concentrations higher than
those necessary to inhibit PG synthesis. Experiments with indomethacin
revealed that the effects of aspirin on DC maturation were
cyclooxygenase independent. Nuclear extracts of purified,
aspirin-treated DC revealed a decreased NF-
B DNA-binding activity,
whereas Ab supershift analysis indicated that aspirin targeted
primarily NF-B p50. Unexpectedly, aspirin promoted the generation of
CD11c+ DC, due to apparent suppression of granulocyte
development. The morphological and ultrastructural appearance of
aspirin-treated cells was consistent with immaturity. Aspirin-treated
DC were highly efficient at Ag capture, via both mannose
receptor-mediated endocytosis and macropinocytosis. By contrast, they
were poor stimulators of naive allogeneic T cell proliferation and
induced lower levels of IL-2 in responding T cells. They also exhibited
impaired IL-12 expression and did not produce IL-10 after LPS
stimulation. Assessment of the in vivo function of aspirin-treated DC,
pulsed with the hapten trinitrobenzenesulfonic acid, revealed an
inability to induce normal cell-mediated contact hypersensitivity,
despite the ability of the cells to migrate to T cell areas of draining
lymphoid tissue. These data provide new insight into the
immunopharmacology of aspirin and suggest a novel approach to the
manipulation of DC for therapeutic application.
This article has been cited by other articles:
|
|
 |
|
  A. Karakawa, Y. Fukawa, M. Okazaki, K. Takahashi, T. Sano, H. Amano, M. Yamamoto, and S. Yamada Diclofenac Sodium Inhibits NF{kappa}B Transcription in Osteoclasts Journal of Dental Research, November 1, 2009; 88(11): 1042 - 1047. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Ponticelli, M. Moia, and G. Montagnino Renal allograft thrombosis Nephrol. Dial. Transplant., May 1, 2009; 24(5): 1388 - 1393. [Full Text] [PDF]
|
|
|
|
 |
|
 H. R. Turnquist, T. L. Sumpter, A. Tsung, A. F. Zahorchak, A. Nakao, G. J. Nau, F. Y. Liew, D. A. Geller, and A. W. Thomson IL-1{beta}-Driven ST2L Expression Promotes Maturation Resistance in Rapamycin-Conditioned Dendritic Cells J. Immunol., July 1, 2008; 181(1): 62 - 72. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. P. A. MacDonald, R. D. Kuns, V. Rowe, E. S. Morris, T. Banovic, H. Bofinger, B. O'Sullivan, K. A. Markey, A. L. Don, R. Thomas, et al. Effector and regulatory T-cell function is differentially regulated by RelB within antigen-presenting cells during GVHD Blood, June 1, 2007; 109(11): 5049 - 5057. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Sen, M. A. Wallet, Z. Yi, Y. Huang, M. Henderson, C. E. Mathews, H. S. Earp, G. Matsushima, A. S. Baldwin Jr, and R. M. Tisch Apoptotic cells induce Mer tyrosine kinase-dependent blockade of NF-{kappa}B activation in dendritic cells Blood, January 15, 2007; 109(2): 653 - 660. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Y. Lan, Z. Wang, G. Raimondi, W. Wu, B. L. Colvin, A. De Creus, and A. W. Thomson "Alternatively Activated" Dendritic Cells Preferentially Secrete IL-10, Expand Foxp3+CD4+ T Cells, and Induce Long-Term Organ Allograft Survival in Combination with CTLA4-Ig J. Immunol., November 1, 2006; 177(9): 5868 - 5877. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. I. Iruretagoyena, S. E. Sepulveda, J. P. Lezana, M. Hermoso, M. Bronfman, M. A. Gutierrez, S. H. Jacobelli, and A. M. Kalergis Inhibition of Nuclear Factor-{kappa}B Enhances the Capacity of Immature Dendritic Cells to Induce Antigen-Specific Tolerance in Experimental Autoimmune Encephalomyelitis J. Pharmacol. Exp. Ther., July 1, 2006; 318(1): 59 - 67. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. F. McCarty and K. I. Block Toward a Core Nutraceutical Program for Cancer Management Integr Cancer Ther, June 1, 2006; 5(2): 150 - 171. [Abstract] [PDF]
|
|
|
|
 |
|
 T. Yokoyama, O. Aramaki, T. Takayama, S. Takano, Q. Zhang, M. Shimazu, M. Kitajima, Y. Ikeda, N. Shirasugi, and M. Niimi Selective cyclooxygenase 2 inhibitor induces indefinite survival of fully allogeneic cardiac grafts and generates CD4+ regulatory cells J. Thorac. Cardiovasc. Surg., October 1, 2005; 130(4): 1167 - 1174. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Rogers, I. Perkins, A. van Olphen, N. Burdash, T. W. Klein, and H. Friedman Epigallocatechin Gallate Modulates Cytokine Production by Bone Marrow-Derived Dendritic Cells Stimulated with Lipopolysaccharide or Muramyldipeptide, or Infected with Legionella pneumophila Experimental Biology and Medicine, October 1, 2005; 230(9): 645 - 651. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G.-Y. Kim, K.-H. Kim, S.-H. Lee, M.-S. Yoon, H.-J. Lee, D.-O. Moon, C.-M. Lee, S.-C. Ahn, Y. C. Park, and Y.-M. Park Curcumin Inhibits Immunostimulatory Function of Dendritic Cells: MAPKs and Translocation of NF-{kappa}B as Potential Targets J. Immunol., June 15, 2005; 174(12): 8116 - 8124. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. P. A. MacDonald, V. Rowe, A. D. Clouston, J. K. Welply, R. D. Kuns, J. L. M. Ferrara, R. Thomas, and G. R. Hill Cytokine Expanded Myeloid Precursors Function as Regulatory Antigen-Presenting Cells and Promote Tolerance through IL-10-Producing Regulatory T Cells J. Immunol., February 15, 2005; 174(4): 1841 - 1850. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Bhattacharyya, P. Sen, M. Wallet, B. Long, A. S. Baldwin Jr, and R. Tisch Immunoregulation of dendritic cells by IL-10 is mediated through suppression of the PI3K/Akt pathway and of I{kappa}B kinase activity Blood, August 15, 2004; 104(4): 1100 - 1109. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. Mirenda, I. Berton, J. Read, T. Cook, J. Smith, A. Dorling, and R. I. Lechler Modified Dendritic Cells Coexpressing Self and Allogeneic Major Histocompatability Complex Molecules: An Efficient Way to Induce Indirect Pathway Regulation J. Am. Soc. Nephrol., April 1, 2004; 15(4): 987 - 997. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Goddard, J. Youster, E. Morgan, and D. H. Adams Interleukin-10 Secretion Differentiates Dendritic Cells from Human Liver and Skin Am. J. Pathol., February 1, 2004; 164(2): 511 - 519. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. Machida, H. Matsuse, Y. Kondo, T. Kawano, S. Saeki, S. Tomari, Y. Obase, C. Fukushima, and S. Kohno Cysteinyl Leukotrienes Regulate Dendritic Cell Functions in a Murine Model of Asthma J. Immunol., February 1, 2004; 172(3): 1833 - 1838. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. T. E. Lim, G. A. Piazza, R. Pamukcu, W. J. Thompson, and I. B. Weinstein Exisulind and Related Compounds Inhibit Expression and Function of the Androgen Receptor in Human Prostate Cancer Cells Clin. Cancer Res., October 15, 2003; 9(13): 4972 - 4982. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Hackstein, T. Taner, A. F. Zahorchak, A. E. Morelli, A. J. Logar, A. Gessner, and A. W. Thomson Rapamycin inhibits IL-4--induced dendritic cell maturation in vitro and dendritic cell mobilization and function in vivo Blood, June 1, 2003; 101(11): 4457 - 4463. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. M. Woltman and C. van Kooten Functional modulation of dendritic cells to suppress adaptive immune responses J. Leukoc. Biol., April 1, 2003; 73(4): 428 - 441. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Andreakos, C. Smith, C. Monaco, F. M. Brennan, B. M. Foxwell, and M. Feldmann Ikappa B kinase 2 but not NF-kappa B-inducing kinase is essential for effective DC antigen presentation in the allogeneic mixed lymphocyte reaction Blood, February 1, 2003; 101(3): 983 - 991. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Eto, H. Hackstein, K. Kaneko, K. Nomoto, and A. W. Thomson Promotion of Skin Graft Tolerance Across MHC Barriers by Mobilization of Dendritic Cells in Donor Hemopoietic Cell Infusions J. Immunol., September 1, 2002; 169(5): 2390 - 2396. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Hackstein, T. Taner, A. J. Logar, and A. W. Thomson Rapamycin inhibits macropinocytosis and mannose receptor-mediated endocytosis by bone marrow-derived dendritic cells Blood, July 18, 2002; 100(3): 1084 - 1087. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. D'Acquisto, M. J. May, and S. Ghosh Inhibition of Nuclear Factor Kappa B (NF-B):: An Emerging Theme in Anti-Inflammatory Therapies Mol. Interv., February 1, 2002; 2(1): 22 - 35. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Poligone, D. J. Weaver Jr., P. Sen, A. S. Baldwin Jr., and R. Tisch Elevated NF-{kappa}B Activation in Nonobese Diabetic Mouse Dendritic Cells Results in Enhanced APC Function J. Immunol., January 1, 2002; 168(1): 188 - 196. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
