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: Role of the p38 and p42/44 Mitogen-Activated Protein Kinases1
Kennedy Institute of Rheumatology, Hammersmith, London, United Kingdom
IL-10 is an anti-inflammatory cytokine with potent
immunomodulatory effects, including inhibition of cytokine production.
However, regulation of monocyte IL-10 production is poorly understood.
In this report we have investigated the mechanisms of LPS-induced IL-10
production by human peripheral blood monocytes and demonstrate that
IL-10 synthesis is uniquely dependent on the endogenous proinflammatory
cytokines IL-1 and/or TNF-
. LPS signal transduction in monocytes has
been shown to involve activation of the p38 and p42 mitogen-activated
protein kinase (MAPK) cascades. The results in this paper indicate that
inhibition of p38 MAPK potently inhibited the production of IL-10,
IL-1ß, and TNF-, whereas blockade of the p42/44 MAPK pathway,
while partially inhibiting TNF- and IL-1ß production, had no
effect on monocyte secretion of IL-10. Furthermore, neither the
inhibition of monocyte TNF- induced by IL-10 nor the stimulation of
soluble TNF receptor production was affected by inhibition of the
p42/44 MAPK pathway, suggesting that this signaling event is not
involved in either monocyte production of or anti-inflammatory
responses to IL-10. These data raise the interesting possibility that
proinflammatory TNF--mediated effects may be selectively blocked
without modulating the induction or the response to IL-10, whereas the
signaling events associated with the anti-inflammatory events
induced by IL-10 remain to be elucidated.
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N. Reiling, A. Blumenthal, H.-D. Flad, M. Ernst, and S. Ehlers Mycobacteria-Induced TNF-{alpha} and IL-10 Formation by Human Macrophages Is Differentially Regulated at the Level of Mitogen-Activated Protein Kinase Activity J. Immunol., September 15, 2001; 167(6): 3339 - 3345. [Abstract] [Full Text] [PDF]
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A. M. Liese, M. Q. Siddiqi, J. H. Siegel, T. Denny, and Z. Spolarics Augmented TNF-{alpha} and IL-10 production by primed human monocytes following interaction with oxidatively modified autologous erythrocytes J. Leukoc. Biol., August 1, 2001; 70(2): 289 - 296. [Abstract] [Full Text] [PDF]
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L. Rabehi, T. Irinopoulou, B. Cholley, N. Haeffner-Cavaillon, and M.-P. Carreno Gram-Positive and Gram-Negative Bacteria Do Not Trigger Monocytic Cytokine Production through Similar Intracellular Pathways Infect. Immun., July 1, 2001; 69(7): 4590 - 4599. [Abstract] [Full Text] [PDF]
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J. Varghese, S. Chattopadhaya, and A. Sarin Inhibition of p38 Kinase Reveals a TNF-{{alpha}}-Mediated, Caspase-Dependent, Apoptotic Death Pathway in a Human Myelomonocyte Cell Line J. Immunol., June 1, 2001; 166(11): 6570 - 6577. [Abstract] [Full Text] [PDF]
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M. H. A. M. Veltrop, J. A. M. Langermans, J. Thompson, and M. J. L. M. F. Bancsi Interleukin-10 Regulates the Tissue Factor Activity of Monocytes in an In Vitro Model of Bacterial Endocarditis Infect. Immun., May 1, 2001; 69(5): 3197 - 3202. [Abstract] [Full Text] [PDF]
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C. Ropert, I. C. Almeida, M. Closel, L. R. Travassos, M. A. J. Ferguson, P. Cohen, and R. T. Gazzinelli Requirement of Mitogen-Activated Protein Kinases and I{{kappa}}B Phosphorylation for Induction of Proinflammatory Cytokines Synthesis by Macrophages Indicates Functional Similarity of Receptors Triggered by Glycosylphosphatidylinositol Anchors from Parasitic Protozoa and Bacterial Lipopolysaccharide J. Immunol., March 1, 2001; 166(5): 3423 - 3431. [Abstract] [Full Text] [PDF]
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T. Matsuoka, H. Tabata, and S. Matsushita Monocytes Are Differentially Activated Through HLA-DR, -DQ, and -DP Molecules Via Mitogen-Activated Protein Kinases J. Immunol., February 15, 2001; 166(4): 2202 - 2208. [Abstract] [Full Text] [PDF]
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K. M. Krishna Rao MAP kinase activation in macrophages J. Leukoc. Biol., January 1, 2001; 69(1): 3 - 10. [Abstract] [Full Text]
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 M. Fujita, J. M. Shannon, C. G. Irvin, K. A. Fagan, C. Cool, A. Augustin, and R. J. Mason Overexpression of tumor necrosis factor-{alpha} produces an increase in lung volumes and pulmonary hypertension Am J Physiol Lung Cell Mol Physiol, January 1, 2001; 280(1): L39 - L49. [Abstract] [Full Text] [PDF]
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D. Stoiber, S. Stockinger, P. Steinlein, J. Kovarik, and T. Decker Listeria monocytogenes Modulates Macrophage Cytokine Responses Through STAT Serine Phosphorylation and the Induction of Suppressor of Cytokine Signaling 3 J. Immunol., January 1, 2001; 166(1): 466 - 472. [Abstract] [Full Text] [PDF]
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D. Stoiber, P. Kovarik, S. Cohney, J. A. Johnston, P. Steinlein, and T. Decker Lipopolysaccharide Induces in Macrophages the Synthesis of the Suppressor of Cytokine Signaling 3 and Suppresses Signal Transduction in Response to the Activating Factor IFN-{gamma} J. Immunol., September 1, 1999; 163(5): 2640 - 2647. [Abstract] [Full Text] [PDF]
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T. van der Bruggen, S. Nijenhuis, E. van Raaij, J. Verhoef, and B. Sweder van Asbeck Lipopolysaccharide-Induced Tumor Necrosis Factor Alpha Production by Human Monocytes Involves the Raf-1/MEK1-MEK2/ERK1-ERK2 Pathway Infect. Immun., August 1, 1999; 67(8): 3824 - 3829. [Abstract] [Full Text] [PDF]
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 J. Bondeson, B. Foxwell, F. Brennan, and M. Feldmann Defining therapeutic targets by using adenovirus: Blocking NF-kappa B inhibits both inflammatory and destructive mechanisms in rheumatoid synovium but spares anti-inflammatory mediators PNAS, May 11, 1999; 96(10): 5668 - 5673. [Abstract] [Full Text] [PDF]
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K. Miura, J. T. Schroeder, W. C. Hubbard, and D. W. MacGlashan Jr. Extracellular Signal-Regulated Kinases Regulate Leukotriene C4 Generation, But Not Histamine Release or IL-4 Production from Human Basophils J. Immunol., April 1, 1999; 162(7): 4198 - 4206. [Abstract] [Full Text] [PDF]
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K. K. Hale, D. Trollinger, M. Rihanek, and C. L. Manthey Differential Expression and Activation of p38 Mitogen-Activated Protein Kinase {alpha}, {beta}, {gamma}, and {delta} in Inflammatory Cell Lineages J. Immunol., April 1, 1999; 162(7): 4246 - 4252. [Abstract] [Full Text] [PDF]
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J. Bondeson, K. A. Browne, F. M. Brennan, B. M. J. Foxwell, and M. Feldmann Selective Regulation of Cytokine Induction by Adenoviral Gene Transfer of I{kappa}B{alpha} into Human Macrophages: Lipopolysaccharide-Induced, But Not Zymosan-Induced, Proinflammatory Cytokines Are Inhibited, But IL-10 Is Nuclear Factor-{kappa}B Independent J. Immunol., March 1, 1999; 162(5): 2939 - 2945. [Abstract] [Full Text] [PDF]
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K. E. Noble, R. G. Wickremasinghe, C. DeCornet, P. Panayiotidis, and K. L. Yong Monocytes Stimulate Expression of the Bcl-2 Family Member, A1, in Endothelial Cells and Confer Protection Against Apoptosis J. Immunol., February 1, 1999; 162(3): 1376 - 1383. [Abstract] [Full Text] [PDF]
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P. H. Schafer, L. Wang, S. A. Wadsworth, J. E. Davis, and J. J. Siekierka T Cell Activation Signals Up-Regulate p38 Mitogen-Activated Protein Kinase Activity and Induce TNF-{alpha} Production in a Manner Distinct from LPS Activation of Monocytes J. Immunol., January 15, 1999; 162(2): 659 - 668. [Abstract] [Full Text] [PDF]
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J. L. E. Dean, M. Brook, A. R. Clark, and J. Saklatvala p38 Mitogen-activated Protein Kinase Regulates Cyclooxygenase-2 mRNA Stability and Transcription in Lipopolysaccharide-treated Human Monocytes J. Biol. Chem., January 1, 1999; 274(1): 264 - 269. [Abstract] [Full Text] [PDF]
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D. D. Browning, N. D. Windes, and R. D. Ye Activation of p38 Mitogen-activated Protein Kinase by Lipopolysaccharide in Human Neutrophils Requires Nitric Oxide-dependent cGMP Accumulation J. Biol. Chem., January 1, 1999; 274(1): 537 - 542. [Abstract] [Full Text] [PDF]
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P. A. Scherle, E. A. Jones, M. F. Favata, A. J. Daulerio, M. B. Covington, S. A. Nurnberg, R. L. Magolda, and J. M. Trzaskos Inhibition of MAP Kinase Kinase Prevents Cytokine and Prostaglandin E2 Production in Lipopolysaccharide-Stimulated Monocytes J. Immunol., November 15, 1998; 161(10): 5681 - 5686. [Abstract] [Full Text] [PDF]
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K. Rutault, C. A. Hazzalin, and L. C. Mahadevan Combinations of ERK and p38 MAPK Inhibitors Ablate Tumor Necrosis Factor-alpha (TNF-alpha ) mRNA Induction. EVIDENCE FOR SELECTIVE DESTABILIZATION OF TNF-alpha TRANSCRIPTS J. Biol. Chem., February 23, 2001; 276(9): 6666 - 6674. [Abstract] [Full Text] [PDF]
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W. Ma, W. Lim, K. Gee, S. Aucoin, D. Nandan, M. Kozlowski, F. Diaz-Mitoma, and A. Kumar The p38 Mitogen-activated Kinase Pathway Regulates the Human Interleukin-10 Promoter via the Activation of Sp1 Transcription Factor in Lipopolysaccharide-stimulated Human Macrophages J. Biol. Chem., April 20, 2001; 276(17): 13664 - 13674. [Abstract] [Full Text] [PDF]
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J.-i. Okano and A. K. Rustgi Paclitaxel Induces Prolonged Activation of the Ras/MEK/ERK Pathway Independently of Activating the Programmed Cell Death Machinery J. Biol. Chem., May 25, 2001; 276(22): 19555 - 19564. [Abstract] [Full Text] [PDF]
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S. Bechoua and L. W. Daniel Phospholipase D Is Required in the Signaling Pathway Leading to p38 MAPK Activation in Neutrophil-like HL-60 Cells, Stimulated by N-Formyl-methionyl-leucyl-phenylalanine J. Biol. Chem., August 17, 2001; 276(34): 31752 - 31759. [Abstract] [Full Text] [PDF]
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Y.-Z. Wang, P. Zhang, A. B. Rice, and J. C. Bonner Regulation of Interleukin-1beta -induced Platelet-derived Growth Factor Receptor-alpha Expression in Rat Pulmonary Myofibroblasts by p38 Mitogen-activated Protein Kinase J. Biol. Chem., July 14, 2000; 275(29): 22550 - 22557. [Abstract] [Full Text] [PDF]
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