| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Departments of
*
Experimental Internal Medicine, and
Infectious Diseases, Tropical Medicine, and AIDS, Academic Medical Center, Amsterdam, The Netherlands
p38 mitogen-activated protein kinase (MAPK) has been suggested as a mediator of cytokine release and is currently being targeted for anti-inflammatory therapy. However, experimental data are contradictory and lack sufficient affirmation in vivo. We tested the effect of p38 MAPK inhibition in several cell types and in different murine models of infectious disease. We observed that most cell types react to p38 MAPK inhibition with diminished cytokine release, but that this treatment induced increased cytokine release in macrophages. Furthermore, we observed increased cytokine production in mouse models of pneumococcal pneumonia and tuberculosis accompanied by severely reduced bacterial clearance. This apparent inefficacy of p38 MAPK inhibition in reducing cytokine release in infectious disease, as well as its immune-compromising action, suggest that targeting p38 MAPK may not be a suitable anti-cytokine strategy in patients with such disease or at risk for infection.
This article has been cited by other articles:
|
|
 |
|
  Y. Chen, C. S. K. Kam, F. Q. Liu, Y. Liu, V. C. H. Lui, J. R. Lamb, and P. K. H. Tam LPS-induced up-regulation of TGF-{beta} receptor 1 is associated with TNF-{alpha} expression in human monocyte-derived macrophages J. Leukoc. Biol., May 1, 2008; 83(5): 1165 - 1173. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Garcia-Herrera, M. C. Marca, E. Brot-Laroche, N. Guillen, S. Acin, M. A. Navarro, J. Osada, and M. J. Rodriguez-Yoldi Protein kinases, TNF-{alpha}, and proteasome contribute in the inhibition of fructose intestinal transport by sepsis in vivo Am J Physiol Gastrointest Liver Physiol, January 1, 2008; 294(1): G155 - G164. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Ipaktchi, A. Mattar, A. D. Niederbichler, L. M. Hoesel, S. Vollmannshauser, M. R. Hemmila, G. L. Su, D. G. Remick, S. C. Wang, and S. Arbabi Attenuating Burn Wound Inflammatory Signaling Reduces Systemic Inflammation and Acute Lung Injury J. Immunol., December 1, 2006; 177(11): 8065 - 8071. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. J. Ratner, K. R. Hippe, J. L. Aguilar, M. H. Bender, A. L. Nelson, and J. N. Weiser Epithelial Cells Are Sensitive Detectors of Bacterial Pore-forming Toxins J. Biol. Chem., May 5, 2006; 281(18): 12994 - 12998. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Inoue, D. L. Boyle, M. Corr, D. Hammaker, R. J. Davis, R. A. Flavell, and G. S. Firestein Mitogen-activated protein kinase kinase 3 is a pivotal pathway regulating p38 activation in inflammatory arthritis PNAS, April 4, 2006; 103(14): 5484 - 5489. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. M. Kuldo, J. Westra, S. A. Asgeirsdottir, R. J. Kok, K. Oosterhuis, M. G. Rots, J. P. Schouten, P. C. Limburg, and G. Molema Differential effects of NF-{kappa}B and p38 MAPK inhibitors and combinations thereof on TNF-{alpha}- and IL-1{beta}-induced proinflammatory status of endothelial cells in vitro Am J Physiol Cell Physiol, November 1, 2005; 289(5): C1229 - C1239. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Schnyder-Candrian, V. F. J. Quesniaux, F. Di Padova, I. Maillet, N. Noulin, I. Couillin, R. Moser, F. Erard, B. B. Vargaftig, B. Ryffel, et al. Dual Effects of p38 MAPK on TNF-Dependent Bronchoconstriction and TNF-Independent Neutrophil Recruitment in Lipopolysaccharide-Induced Acute Respiratory Distress Syndrome J. Immunol., July 1, 2005; 175(1): 262 - 269. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Knapp, S. Gibot, A. de Vos, H. H. Versteeg, M. Colonna, and T. van der Poll Cutting Edge: Expression Patterns of Surface and Soluble Triggering Receptor Expressed on Myeloid Cells-1 in Human Endotoxemia J. Immunol., December 15, 2004; 173(12): 7131 - 7134. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. I. Rennard Antiinflammatory Therapies Other Than Corticosteroids Proceedings of the ATS, November 1, 2004; 1(3): 282 - 287. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D.-G. Cho, M. R. Mulloy, P. A. Chang, M. D. Johnson, A. S. Aharon, T. A. Robison, T. L. Buckles, D. W. Byrne, and D. C. Drinkwater Jr Blockade of the extracellular signal-regulated kinase pathway by U0126 attenuates neuronal damage following circulatory arrest J. Thorac. Cardiovasc. Surg., April 1, 2004; 127(4): 1033 - 1040. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. C. Aird The role of the endothelium in severe sepsis and multiple organ dysfunction syndrome Blood, May 15, 2003; 101(10): 3765 - 3777. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. A. Nick, S. K. Young, P. G. Arndt, J. G. Lieber, B. T. Suratt, K. R. Poch, N. J. Avdi, K. C. Malcolm, C. Taube, P. M. Henson, et al. Selective Suppression of Neutrophil Accumulation in Ongoing Pulmonary Inflammation by Systemic Inhibition of p38 Mitogen-Activated Protein Kinase J. Immunol., November 1, 2002; 169(9): 5260 - 5269. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Takanami-Ohnishi, S. Amano, S. Kimura, S. Asada, A. Utani, M. Maruyama, H. Osada, H. Tsunoda, Y. Irukayama-Tomobe, K. Goto, et al. Essential Role of p38 Mitogen-activated Protein Kinase in Contact Hypersensitivity J. Biol. Chem., September 27, 2002; 277(40): 37896 - 37903. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Arcaroli, K.-Y. Yang, H.-K. Yum, J. Kupfner, T. M. Pitts, J. S. Park, D. Strassheim, and E. Abraham Effects of catecholamines on kinase activation in lung neutrophils after hemorrhage or endotoxemia J. Leukoc. Biol., September 1, 2002; 72(3): 571 - 579. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. D. Lehner, F. Schwoebel, A. Kotlyarov, M. Leist, M. Gaestel, and T. Hartung Mitogen-Activated Protein Kinase-Activated Protein Kinase 2-Deficient Mice Show Increased Susceptibility to Listeria monocytogenes Infection J. Immunol., May 1, 2002; 168(9): 4667 - 4673. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Branger, B. van den Blink, S. Weijer, J. Madwed, C. L. Bos, A. Gupta, C.-L. Yong, S. H. Polmar, D. P. Olszyna, C. E. Hack, et al. Anti-Inflammatory Effects of a p38 Mitogen-Activated Protein Kinase Inhibitor During Human Endotoxemia J. Immunol., April 15, 2002; 168(8): 4070 - 4077. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T ten Hove, B van den Blink, I Pronk, P Drillenburg, M P Peppelenbosch, and S J H van Deventer Dichotomal role of inhibition of p38 MAPK with SB 203580 in experimental colitis Gut, April 1, 2002; 50(4): 507 - 512. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Carballo, H. Cao, W. S. Lai, E. A. Kennington, D. Campbell, and P. J. Blackshear Decreased Sensitivity of Tristetraprolin-deficient Cells to p38 Inhibitors Suggests the Involvement of Tristetraprolin in the p38 Signaling Pathway J. Biol. Chem., November 2, 2001; 276(45): 42580 - 42587. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
