| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
*
Department of Pharmacological and Physiological Sciences, and
Department of Molecular Microbiology and Immunology, St. Louis University School of Medicine, St. Louis, MO 63104
Several reports have shown that bicyclic imidazoles, specific
inhibitors of the p38 mitogen-activated protein kinase (MAPK), block
cytokine synthesis at the translational level. In this study, we
examined the role of p38 MAPK in the regulation of the IL-1ß cytokine
gene in monocytic cell lines using the bicyclic imidazole SB203580.
Addition of SB203580 30 min before stimulation of monocytes with LPS
inhibited IL-1ß protein and steady state message in a dose-dependent
manner in both RAW264.7 and J774 cell lines. The loss of IL-1ß
message was due mainly to inhibition of transcription, since nuclear
run-off analysis showed an 
80% decrease in specific IL-1 RNA
synthesis. In contrast, SB203580 had no effect on the synthesis of
TNF-
message. LPS-stimulated p38 MAPK activity in the RAW264.7 cells
was blocked by SB203580, as measured by the inhibition of MAPKAP2
kinase activity, a downstream target of the p38 MAPK. CCAATT/enhancer
binding protein (C/EBP)/NFIL-6-driven chloramphenicol acetyltransferase
(CAT) reporter activity was sensitive to SB203580, indicating that
C/EBP/NFIL-6 transcription factor(s) are also targets of p38 MAPK. In
contrast, transfected CAT constructs containing NF-
B elements were
only partially inhibited (35%) at the highest concentration of
SB203580 after LPS stimulation. As measured by EMSA, LPS-stimulated
NF-B activation was not affected by SB203580. Overall, the results
demonstrate, for the first time, a role for p38 MAPK in IL-1ß
transcription by acting through C/EBP/NFIL-6 transcription
factors.
This article has been cited by other articles:
|
|
 |
|
  Y. Zhang, S. Saccani, H. Shin, and B. S. Nikolajczyk Dynamic Protein Associations Define Two Phases of IL-1{beta} Transcriptional Activation J. Immunol., July 1, 2008; 181(1): 503 - 512. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. J. Kang, J. Chen, M. Otsuka, J. Mols, S. Ren, Y. Wang, and J. Han Macrophage Deletion of p38{alpha} Partially Impairs Lipopolysaccharide-Induced Cellular Activation J. Immunol., April 1, 2008; 180(7): 5075 - 5082. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Thalhamer, M. A. McGrath, and M. M. Harnett MAPKs and their relevance to arthritis and inflammation Rheumatology, April 1, 2008; 47(4): 409 - 414. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Salojin and T. Oravecz Regulation of innate immunity by MAPK dual-specificity phosphatases: knockout models reveal new tricks of old genes J. Leukoc. Biol., April 1, 2007; 81(4): 860 - 869. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S.-H. Kim, C.-D. Jun, K. Suk, B.-J. Choi, H. Lim, S. Park, S. H. Lee, H.-Y. Shin, D.-K. Kim, and T.-Y. Shin Gallic Acid Inhibits Histamine Release and Pro-inflammatory Cytokine Production in Mast Cells Toxicol. Sci., May 1, 2006; 91(1): 123 - 131. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. D. Liang, Y. Zhang, D. McDevit, S. Marecki, and B. S. Nikolajczyk The Interleukin-1beta Gene Is Transcribed from a Poised Promoter Architecture in Monocytes J. Biol. Chem., April 7, 2006; 281(14): 9227 - 9237. [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]
|
|
|
|
 |
|
 C.-Y. Yeh, J.-Y. Chen, and J.-S. Chia Glucosyltransferases of Viridans Group Streptococci Modulate Interleukin-6 and Adhesion Molecule Expression in Endothelial Cells and Augment Monocytic Cell Adherence Infect. Immun., February 1, 2006; 74(2): 1273 - 1283. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. V. Salojin, I. B. Owusu, K. A. Millerchip, M. Potter, K. A. Platt, and T. Oravecz Essential Role of MAPK Phosphatase-1 in the Negative Control of Innate Immune Responses J. Immunol., February 1, 2006; 176(3): 1899 - 1907. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Hayer, G. Steiner, B. Gortz, E. Reiter, M. Tohidast-Akrad, M. Amling, O. Hoffmann, K. Redlich, J. Zwerina, K. Skriner, et al. CD44 is a determinant of inflammatory bone loss J. Exp. Med., March 21, 2005; 201(6): 903 - 914. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S.-H. Kim, C.-H. Choi, S.-Y. Kim, J.-S. Eun, and T.-Y. Shin Anti-Allergic Effects of Artemisia iwayomogi on Mast Cell-Mediated Allergy Model Experimental Biology and Medicine, January 1, 2005; 230(1): 82 - 88. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. G. Shepherd, Q. Zhao, S. E. Welty, T. N. Hansen, C. V. Smith, and Y. Liu The Function of Mitogen-activated Protein Kinase Phosphatase-1 in Peptidoglycan-stimulated Macrophages J. Biol. Chem., December 24, 2004; 279(52): 54023 - 54031. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Campbell, C. J. Ciesielski, A. E. Hunt, N. J. Horwood, J. T. Beech, L. A. Hayes, A. Denys, M. Feldmann, F. M. Brennan, and B. M. J. Foxwell A Novel Mechanism for TNF-{alpha} Regulation by p38 MAPK: Involvement of NF-{kappa}B with Implications for Therapy in Rheumatoid Arthritis J. Immunol., December 1, 2004; 173(11): 6928 - 6937. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. M. Weber, K. T. Chambers, K. G. Bensch, A. L. Scarim, and J. A. Corbett PPAR{gamma} ligands induce ER stress in pancreatic {beta}-cells: ER stress activation results in attenuation of cytokine signaling Am J Physiol Endocrinol Metab, December 1, 2004; 287(6): E1171 - E1177. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Tanaka, T. Morita, A. Nezu, A. Tanimura, I. Mizoguchi, and Y. Tojyo Signaling Mechanisms Involved in Protease-Activated Receptor-1-Mediated Interleukin-6 Production by Human Gingival Fibroblasts J. Pharmacol. Exp. Ther., November 1, 2004; 311(2): 778 - 786. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. A. Brooks, J. E. Connolly, and W. F. C. Rigby The Role of mRNA Turnover in the Regulation of Tristetraprolin Expression: Evidence for an Extracellular Signal-Regulated Kinase-Specific, AU-Rich Element-Dependent, Autoregulatory Pathway J. Immunol., June 15, 2004; 172(12): 7263 - 7271. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. A. Godambe, K. M. Knapp, E. A. Meals, and B. K. English Role of vav1 in the Lipopolysaccharide-Mediated Upregulation of Inducible Nitric Oxide Synthase Production and Nuclear Factor for Interleukin-6 Expression Activity in Murine Macrophages Clin. Vaccine Immunol., May 1, 2004; 11(3): 525 - 531. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Kelicen and N. Tindberg Lipopolysaccharide Induces CYP2E1 in Astrocytes through MAP Kinase Kinase-3 and C/EBP{beta} and -{delta} J. Biol. Chem., April 16, 2004; 279(16): 15734 - 15742. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. M. Weber, A. L. Scarim, and J. A. Corbett PPAR{gamma} is not required for the inhibitory actions of PGJ2 on cytokine signaling in pancreatic {beta}-cells Am J Physiol Endocrinol Metab, March 1, 2004; 286(3): E329 - E336. [Abstract] [Full Text]
|
|
|
|
 |
|
 X. Li, N. Udagawa, M. Takami, N. Sato, Y. Kobayashi, and N. Takahashi p38 Mitogen-Activated Protein Kinase Is Crucially Involved in Osteoclast Differentiation But Not in Cytokine Production, Phagocytosis, or Dendritic Cell Differentiation of Bone Marrow Macrophages Endocrinology, November 1, 2003; 144(11): 4999 - 5005. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y.-W. Liu, H.-P. Tseng, L.-C. Chen, B.-K. Chen, and W.-C. Chang Functional Cooperation of Simian Virus 40 Promoter Factor 1 and CCAAT/Enhancer-Binding Protein {beta} and {delta} in Lipopolysaccharide-Induced Gene Activation of IL-10 in Mouse Macrophages J. Immunol., July 15, 2003; 171(2): 821 - 828. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. Guo, R. E. Gerl, and J. W. Schrader Defining the Involvement of p38{alpha} MAPK in the Production of Anti- and Proinflammatory Cytokines Using an SB 203580-resistant Form of the Kinase J. Biol. Chem., June 13, 2003; 278(25): 22237 - 22242. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. B. Maggi Jr., J. M. Moran, R. M. L. Buller, and J. A. Corbett ERK Activation Is Required for Double-stranded RNA- and Virus-induced Interleukin-1 Expression by Macrophages J. Biol. Chem., May 2, 2003; 278(19): 16683 - 16689. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Ronni, V. Agarwal, M. Haykinson, M. E. Haberland, G. Cheng, and S. T. Smale Common Interaction Surfaces of the Toll-Like Receptor 4 Cytoplasmic Domain Stimulate Multiple Nuclear Targets Mol. Cell. Biol., April 1, 2003; 23(7): 2543 - 2555. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. A. Parasrampuria, P. de Boer, D. Desai-Krieger, A. T. Chow, and C. R. Jones Single-Dose Pharmacokinetics and Pharmacodynamics of RWJ 67657, a Specific p38 Mitogen-Activated Protein Kinase Inhibitor: A First-in-Human Study J. Clin. Pharmacol., April 1, 2003; 43(4): 406 - 413. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. B. Maggi Jr., J. M. Moran, A. L. Scarim, D. A. Ford, J.-W. Yoon, J. McHowat, R. M. L. Buller, and J. A. Corbett Novel Role for Calcium-independent Phospholipase A2 in the Macrophage Antiviral Response of Inducible Nitric-oxide Synthase Expression J. Biol. Chem., October 4, 2002; 277(41): 38449 - 38455. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. MacKenzie, N. Fernandez-Troy, and E. Espel Post-transcriptional regulation of TNF-{alpha} during in vitro differentiation of human monocytes/macrophages in primary culture J. Leukoc. Biol., June 1, 2002; 71(6): 1026 - 1032. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. N. Finck and R. W. Johnson Anti-inflammatory agents inhibit the induction of leptin by tumor necrosis factor-alpha Am J Physiol Regulatory Integrative Comp Physiol, May 1, 2002; 282(5): R1429 - R1435. [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]
|
|
|
|
|
|
Y. Q. Xiao, K. Malcolm, G. S. Worthen, S. Gardai, W. P. Schiemann, V. A. Fadok, D. L. Bratton, and P. M. Henson Cross-talk between ERK and p38 MAPK Mediates Selective Suppression of Pro-inflammatory Cytokines by Transforming Growth Factor-beta J. Biol. Chem., April 19, 2002; 277(17): 14884 - 14893. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Pfeilschifter, R. Koditz, M. Pfohl, and H. Schatz Changes in Proinflammatory Cytokine Activity after Menopause Endocr. Rev., February 1, 2002; 23(1): 90 - 119. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S.J. Webb, J.R. McPherson, K. Pahan, and S. Koka Regulation of TNF-{alpha}-induced IL-6 Production in MG-63 Human Osteoblast-like Cells J. Dent. Res., January 1, 2002; 81(1): 17 - 22. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Shimomura, M. Matsuura, S. Saito, Y. Hirai, Y. Isshiki, and K. Kawahara Lipopolysaccharide of Burkholderia cepacia and Its Unique Character To Stimulate Murine Macrophages with Relative Lack of Interleukin-1{beta}-Inducing Ability Infect. Immun., June 1, 2001; 69(6): 3663 - 3669. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J.-F. Arrighi, M. Rebsamen, F. Rousset, V. Kindler, and C. Hauser A Critical Role for p38 Mitogen-Activated Protein Kinase in the Maturation of Human Blood-Derived Dendritic Cells Induced by Lipopolysaccharide, TNF-{{alpha}}, and Contact Sensitizers J. Immunol., March 15, 2001; 166(6): 3837 - 3845. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Schmidt, E. Caron, and A. Hall Lipopolysaccharide-Induced Activation of {beta}2-Integrin Function in Macrophages Requires Irak Kinase Activity, p38 Mitogen- Activated Protein Kinase, and the Rap1 GTPase Mol. Cell. Biol., January 15, 2001; 21(2): 438 - 448. [Abstract] [Full Text]
|
|
|
|
|
|
B. van den Blink, N. P. Juffermans, T. ten Hove, M. J. Schultz, S. J. H. van Deventer, T. van der Poll, and M. P. Peppelenbosch p38 Mitogen-Activated Protein Kinase Inhibition Increases Cytokine Release by Macrophages In Vitro and During Infection In Vivo J. Immunol., January 1, 2001; 166(1): 582 - 587. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Ohashi, A. Matsumori, Y. Furukawa, K. Ono, M. Okada, A. Iwasaki, T. Miyamoto, A. Nakano, and S. Sasayama Role of p38 Mitogen-Activated Protein Kinase in Neointimal Hyperplasia After Vascular Injury Arterioscler. Thromb. Vasc. Biol., December 1, 2000; 20(12): 2521 - 2526. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. Lakics, A. E. Medvedev, S. Okada, and S. N. Vogel Inhibition of LPS-induced Cytokines by Bcl-xL in a Murine Macrophage Cell Line J. Immunol., September 1, 2000; 165(5): 2729 - 2737. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Y. Tsai, J. V. Falvo, A. V. Tsytsykova, A. K. Barczak, A. M. Reimold, L. H. Glimcher, M. J. Fenton, D. C. Gordon, I. F. Dunn, and A. E. Goldfeld A Lipopolysaccharide-Specific Enhancer Complex Involving Ets, Elk-1, Sp1, and CREB Binding Protein and p300 Is Recruited to the Tumor Necrosis Factor Alpha Promoter In Vivo Mol. Cell. Biol., August 15, 2000; 20(16): 6084 - 6094. [Abstract] [Full Text]
|
|
|
|
|
|
Y. J. Jeon, Y. K. Kim, M. Lee, S. M. Park, S. B. Han, and H. M. Kim Radicicol Suppresses Expression of Inducible Nitric-Oxide Synthase by Blocking p38 Kinase and Nuclear Factor-kappa B/Rel in Lipopolysaccharide-Stimulated Macrophages J. Pharmacol. Exp. Ther., August 1, 2000; 294(2): 548 - 554. [Abstract] [Full Text]
|
|
|
|
|
|
W. Zhu, J. S. Downey, J. Gu, F. Di Padova, H. Gram, and J. Han Regulation of TNF Expression by Multiple Mitogen-Activated Protein Kinase Pathways J. Immunol., June 15, 2000; 164(12): 6349 - 6358. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Rezzonico, R. Chicheportiche, V. Imbert, and J.-M. Dayer Engagement of CD11b and CD11c beta 2 integrin by antibodies or soluble CD23 induces IL-1beta production on primary human monocytes through mitogen-activated protein kinase-dependent pathways Blood, June 15, 2000; 95(12): 3868 - 3877. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. M. Ndengele, C. J. Bellone, A. J. Lechner, and G. M. Matuschak Brief hypoxia differentially regulates LPS-induced IL-1beta and TNF-alpha gene transcription in RAW 264.7 cells Am J Physiol Lung Cell Mol Physiol, June 1, 2000; 278(6): L1289 - L1296. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. K. Harris, C. M. Coticchia, B. L. Kagan, S. Ahmad, A. Wellstein, and A. T. Riegel Induction of the Angiogenic Modulator Fibroblast Growth Factor-binding Protein by Epidermal Growth Factor Is Mediated through Both MEK/ERK and p38 Signal Transduction Pathways J. Biol. Chem., April 6, 2000; 275(15): 10802 - 10811. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. T. Akama and L. J. Van Eldik beta -Amyloid Stimulation of Inducible Nitric-oxide Synthase in Astrocytes Is Interleukin-1beta - and Tumor Necrosis Factor-alpha (TNFalpha )-dependent, and Involves a TNFalpha Receptor-associated Factor- and NFkappa B-inducing Kinase-dependent Signaling Mechanism J. Biol. Chem., March 10, 2000; 275(11): 7918 - 7924. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. S. Iordanov, J. M. Paranjape, A. Zhou, J. Wong, B. R. G. Williams, E. F. Meurs, R. H. Silverman, and B. E. Magun Activation of p38 Mitogen-Activated Protein Kinase and c-Jun NH2-Terminal Kinase by Double-Stranded RNA and Encephalomyocarditis Virus: Involvement of RNase L, Protein Kinase R, and Alternative Pathways Mol. Cell. Biol., January 15, 2000; 20(2): 617 - 627. [Abstract] [Full Text]
|
|
|
|
|
|
E. Cario, I. M. Rosenberg, S. L. Brandwein, P. L. Beck, H.-C. Reinecker, and D. K. Podolsky Lipopolysaccharide Activates Distinct Signaling Pathways in Intestinal Epithelial Cell Lines Expressing Toll-Like Receptors J. Immunol., January 15, 2000; 164(2): 966 - 972. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. A. Wadsworth, D. E. Cavender, S. A. Beers, P. Lalan, P. H. Schafer, E. A. Malloy, W. Wu, B. Fahmy, G. C. Olini, J. E. Davis, et al. RWJ 67657, a Potent, Orally Active Inhibitor of p38 Mitogen-Activated Protein Kinase J. Pharmacol. Exp. Ther., November 1, 1999; 291(2): 680 - 687. [Abstract] [Full Text]
|
|
|
|
|
|
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]
|
|
|
|
|
|
M. Cattaruzza, I. Eberhardt, and M. Hecker Mechanosensitive Transcription Factors Involved in Endothelin B Receptor Expression J. Biol. Chem., September 28, 2001; 276(40): 36999 - 37003. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
