| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
*
Department of Medicine B,
Institute for Immunology, University of Münster, Münster, Germany
Glucocorticoids (GC) are potent anti-inflammatory and
immunosuppressive agents that act on a variety of immune cells,
including monocytes and macrophages. However, the exact cellular
mechanisms underlying this anti-inflammatory capacity are still
unknown. In our study, we determined the induction of apoptosis by GC
in human monocytes. Peripheral blood monocytes were isolated by density
centrifugation methods with a purity of >90% and were cultured in
RPMI 1640 medium. Monocyte apoptosis was determined by four independent
methods, including annexin-V staining, TUNEL, DNA-laddering, and
typical morphology by means of transmission electron microscopy.
TNF-
and IL-1ß were measured by ELISA. GC receptor was blocked
with mifepristone. Caspase 3 was inhibited with caspase-3 inhibitor
(DEVD-CHO). Stimulation with different GC at therapeutic concentrations
resulted in monocyte apoptosis in a time- and dose-dependent manner.
Necrosis was excluded by propidium iodide staining. Proinflammatory
cytokines such as IL-1ß and TNF- were down-regulated by GC
treatment. Continuous treatment of monocytes with IL-1ß, but not with
TNF-, could almost completely prevent GC-induced cell death. The
addition of mifepristone or caspase-3 inhibitor could partially
abrogate GC-induced apoptosis as well as GC-induced inhibition of
IL-1ß. This is the first study to demonstrate induction of apoptosis
by GC in human monocytes. GC-induced monocyte apoptosis may be
partially mediated through effects on IL-1ß production. It is
conceivable that GC exert their anti-inflammatory capacity in
various diseases, at least in part, by the induction of apoptosis in
monocytes.
This article has been cited by other articles:
|
|
 |
|
  A. Drewniak, B. J. van Raam, J. Geissler, A. T.J. Tool, O. R.F. Mook, T. K. van den Berg, F. Baas, and T. W. Kuijpers Changes in gene expression of granulocytes during in vivo granulocyte colony-stimulating factor/dexamethasone mobilization for transfusion purposes Blood, June 4, 2009; 113(23): 5979 - 5998. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J.-M. Lee, P. Yan, Q. Xiao, S. Chen, K.-Y. Lee, C. Y. Hsu, and J. Xu Methylprednisolone Protects Oligodendrocytes But Not Neurons after Spinal Cord Injury J. Neurosci., March 19, 2008; 28(12): 3141 - 3149. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C.-Y. Yang, T.-H. Kuo, and L.-P. Ting Human Hepatitis B Viral e Antigen Interacts with Cellular Interleukin-1 Receptor Accessory Protein and Triggers Interleukin-1 Response J. Biol. Chem., November 10, 2006; 281(45): 34525 - 34536. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. R. Ritter, J. Reinisch, S. F. Friedlander, and M. Friedlander Myeloid Cells in Infantile Hemangioma Am. J. Pathol., February 1, 2006; 168(2): 621 - 628. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Wada, J. W. Pippin, C. B. Marshall, S. V. Griffin, and S. J. Shankland Dexamethasone Prevents Podocyte Apoptosis Induced by Puromycin Aminonucleoside: Role of p53 and Bcl-2-Related Family Proteins J. Am. Soc. Nephrol., September 1, 2005; 16(9): 2615 - 2625. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Jiang and D. S. Pisetsky The Effect of Dexamethasone on the Generation of Plasma DNA from Dead and Dying Cells Am. J. Pathol., May 1, 2004; 164(5): 1751 - 1759. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. Tommasini and O. Cantoni Dexamethasone Promotes Toxicity in U937 Cells Exposed to Otherwise Nontoxic Concentrations of Peroxynitrite: Pivotal Role for Lipocortin 1-Mediated Inhibition of Cytosolic Phospholipase A2 Mol. Pharmacol., April 1, 2004; 65(4): 964 - 972. [Abstract] [Full Text]
|
|
|
|
 |
|
 F. Dayyani, K.-U. Belge, M. Frankenberger, M. Mack, T. Berki, and L. Ziegler-Heitbrock Mechanism of glucocorticoid-induced depletion of human CD14+CD16+ monocytes J. Leukoc. Biol., July 1, 2003; 74(1): 33 - 39. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. de Baey, I. Mende, G. Baretton, A. Greiner, W. H. Hartl, P. A. Baeuerle, and H. M. Diepolder A Subset of Human Dendritic Cells in the T Cell Area of Mucosa-Associated Lymphoid Tissue with a High Potential to Produce TNF-{alpha} J. Immunol., May 15, 2003; 170(10): 5089 - 5094. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. A. Hintz, A. J. Rassias, K. Wardwell, M. L. Moss, P. M. Morganelli, P. A. Pioli, A. L. Givan, P. K. Wallace, M. P. Yeager, and P. M. Guyre Endotoxin induces rapid metalloproteinase-mediated shedding followed by up-regulation of the monocyte hemoglobin scavenger receptor CD163 J. Leukoc. Biol., October 1, 2002; 72(4): 711 - 717. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Sasson and A. Amsterdam Stimulation of Apoptosis in Human Granulosa Cells from in Vitro Fertilization Patients and Its Prevention by Dexamethasone: Involvement of Cell Contact and Bcl-2 Expression J. Clin. Endocrinol. Metab., July 1, 2002; 87(7): 3441 - 3451. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. M. Woltman, C. Massacrier, J. W. de Fijter, C. Caux, and C. van Kooten Corticosteroids Prevent Generation of CD34+-Derived Dermal Dendritic Cells But Do Not Inhibit Langerhans Cell Development J. Immunol., June 15, 2002; 168(12): 6181 - 6188. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Letuve, A. Druilhe, M. Grandsaigne, M. Aubier, and M. Pretolani Critical Role of Mitochondria, but Not Caspases, during Glucocorticosteroid-Induced Human Eosinophil Apoptosis Am. J. Respir. Cell Mol. Biol., May 1, 2002; 26(5): 565 - 571. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 U. Joashi, S. M. Tibby, C. Turner, A. Mayer, C. Austin, D. Anderson, A. Durward, and I. A. Murdoch Soluble Fas may be a proinflammatory marker after cardiopulmonary bypass in children J. Thorac. Cardiovasc. Surg., January 1, 2002; 123(1): 137 - 144. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Nishimura, N. Nonomura, E. Satoh, Y. Harada, M. Nakayama, T. Tokizane, T. Fukui, Y. Ono, H. Inoue, M. Shin, et al. Potential Mechanism for the Effects of Dexamethasone on Growth of Androgen-Independent Prostate Cancer J Natl Cancer Inst, November 21, 2001; 93(22): 1739 - 1746. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. M. Giles, K. Ross, A. G. Rossi, N. A. Hotchin, C. Haslett, and I. Dransfield Glucocorticoid Augmentation of Macrophage Capacity for Phagocytosis of Apoptotic Cells Is Associated with Reduced p130Cas Expression, Loss of Paxillin/pyk2 Phosphorylation, and High Levels of Active Rac J. Immunol., July 15, 2001; 167(2): 976 - 986. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. D. Kim, Y.-K. Choe, I. S. Choe, and J.-S. Lim Inhibition of glucocorticoid-mediated, caspase-independent dendritic cell death by CD40 activation J. Leukoc. Biol., March 1, 2001; 69(3): 426 - 434. [Abstract] [Full Text]
|
|
|
|
 |
|
 R. Sasson, K. Tajima, and A. Amsterdam Glucocorticoids Protect against Apoptosis Induced by Serum Deprivation, Cyclic Adenosine 3',5'-Monophosphate and p53 Activation in Immortalized Human Granulosa Cells: Involvement of Bcl-2 Endocrinology, February 1, 2001; 142(2): 802 - 811. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Schmidt, N. Lugering, A. Lugering, H.-G. Pauels, K. Schulze-Osthoff, W. Domschke, and T. Kucharzik Role of the CD95/CD95 Ligand System in Glucocorticoid-Induced Monocyte Apoptosis J. Immunol., January 15, 2001; 166(2): 1344 - 1351. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Newton Molecular mechanisms of glucocorticoid action: what is important? Thorax, July 1, 2000; 55(7): 603 - 613. [Full Text]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
