Blood online
Home About Blood Authors Subscriptions Permission Advertising Public Access contact us
 

 
Advanced
Current Issue
First Edition
Archives
Submit to Blood
Search
American Society of Hematology
Meeting Abstracts
Email Alerts
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Right arrow Rights and Permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via CrossRef
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Goebeler, M.
Right arrow Articles by Ludwig, S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Goebeler, M.
Right arrow Articles by Ludwig, S.
Related Collections
Right arrow Hemostasis, Thrombosis, and Vascular Biology
Social Bookmarking
 Add to CiteULike   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?

arrow to previous article Previous Article  |  Table of Contents  |  Next Article next article arrow

Blood, Vol. 93 No. 3 (February 1), 1999: pp. 857-865

The MKK6/p38 Stress Kinase Cascade Is Critical for Tumor Necrosis Factor-alpha -Induced Expression of Monocyte-Chemoattractant Protein-1 in Endothelial Cells

Matthias Goebeler, Karin Kilian, Reinhard Gillitzer, Manfred Kunz, Teizo Yoshimura, Eva-B. Bröcker, Ulf R. Rapp, and Stephan Ludwig

From the Klinik und Poliklinik für Haut- und Geschlechtskrankheiten and Institut für Medizinische Strahlenkunde und Zellforschung (MSZ), Universität Würzburg, Würzburg, Germany; and the Immunopathology Section, Laboratory of Immunobiology, National Cancer Institute-Frederick, Frederick, MD.

Monocyte chemoattractant protein-1 (MCP-1), a member of the C-C subfamily of chemokines, is important for the local recruitment of leukocytes to sites of inflammatory challenge. Here, we investigated endothelial signaling pathways involving members of the mitogen-activated protein (MAP) kinase superfamily and studied their role for MCP-1 expression in endothelium. We show that tumor necrosis factor-alpha (TNF-alpha ), a potent inflammatory activator of endothelium, leads to activation of MAP kinases ERK, p38, and JNK in human umbilical vein endothelial cells (HUVEC). Contribution of MAP kinase pathways to TNF-alpha -induced synthesis of endothelial MCP-1 was then studied by pharmacologic inhibition and transient expression of dominant negative or constitutively active kinase mutants using flow cytometry, Northern blot, and luciferase reporter gene assays. Inhibition of Raf/MEK/ERK or SEK/JNK pathways had no significant effect on MCP-1 levels, whereas blocking the MKK6/p38 pathway by p38 inhibitors SB203580 or SB202190 or by a dominant negative mutant of MKK6, the upstream activator of p38, strongly inhibited TNF-alpha -induced expression of MCP-1. Consistent with that finding, expression of wild-type or constitutively active MKK6 significantly enhanced the effect of limiting TNF-alpha concentrations on MCP-1 synthesis. These data suggest a crucial role for the MKK6/p38 stress kinase cascade in TNF-alpha -mediated endothelial MCP-1 expression.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?


This article has been cited by other articles:


Home page
Ann Rheum DisHome page
G Schett, J Zwerina, and G Firestein
The p38 mitogen-activated protein kinase (MAPK) pathway in rheumatoid arthritis
Ann Rheum Dis, July 1, 2008; 67(7): 909 - 916.
[Abstract] [Full Text] [PDF]


Home page
Am. J. Physiol. Heart Circ. Physiol.Home page
M. Takahashi, E. Suzuki, R. Takeda, S. Oba, H. Nishimatsu, K. Kimura, T. Nagano, R. Nagai, and Y. Hirata
Angiotensin II and tumor necrosis factor-{alpha} synergistically promote monocyte chemoattractant protein-1 expression: roles of NF-{kappa}B, p38, and reactive oxygen species
Am J Physiol Heart Circ Physiol, June 1, 2008; 294(6): H2879 - H2888.
[Abstract] [Full Text] [PDF]


Home page
J. Leukoc. Biol.Home page
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]


Home page
Infect. Immun.Home page
M. K. Stone, G. L. Kolling, M. H. Lindner, and T. G. Obrig
p38 Mitogen-Activated Protein Kinase Mediates Lipopolysaccharide and Tumor Necrosis Factor Alpha Induction of Shiga Toxin 2 Sensitivity in Human Umbilical Vein Endothelial Cells
Infect. Immun., March 1, 2008; 76(3): 1115 - 1121.
[Abstract] [Full Text] [PDF]


Home page
J. Immunol.Home page
V. Muller, D. Viemann, M. Schmidt, N. Endres, S. Ludwig, M. Leverkus, J. Roth, and M. Goebeler
Candida albicans Triggers Activation of Distinct Signaling Pathways to Establish a Proinflammatory Gene Expression Program in Primary Human Endothelial Cells
J. Immunol., December 15, 2007; 179(12): 8435 - 8445.
[Abstract] [Full Text] [PDF]


Home page
J. Immunol.Home page
T. Yoshimura and M. Takahashi
IFN-{gamma}-Mediated Survival Enables Human Neutrophils to Produce MCP-1/CCL2 in Response to Activation by TLR Ligands
J. Immunol., August 1, 2007; 179(3): 1942 - 1949.
[Abstract] [Full Text] [PDF]


Home page
J. Exp. Med.Home page
M. M. Gorska, Q. Liang, S. J. Stafford, N. Goplen, N. Dharajiya, L. Guo, S. Sur, M. Gaestel, and R. Alam
MK2 controls the level of negative feedback in the NF-{kappa}B pathway and is essential for vascular permeability and airway inflammation
J. Exp. Med., July 9, 2007; 204(7): 1637 - 1652.
[Abstract] [Full Text] [PDF]


Home page
J. Immunol.Home page
D. Viemann, M. Schmidt, K. Tenbrock, S. Schmid, V. Muller, K. Klimmek, S. Ludwig, J. Roth, and M. Goebeler
The Contact Allergen Nickel Triggers a Unique Inflammatory and Proangiogenic Gene Expression Pattern via Activation of NF-{kappa}B and Hypoxia-Inducible Factor-1{alpha}
J. Immunol., March 1, 2007; 178(5): 3198 - 3207.
[Abstract] [Full Text] [PDF]


Home page
J. Immunol.Home page
D. K. R. Karaolis, T. K. Means, D. Yang, M. Takahashi, T. Yoshimura, E. Muraille, D. Philpott, J. T. Schroeder, M. Hyodo, Y. Hayakawa, et al.
Bacterial c-di-GMP Is an Immunostimulatory Molecule
J. Immunol., February 15, 2007; 178(4): 2171 - 2181.
[Abstract] [Full Text] [PDF]


Home page
J. Clin. Endocrinol. Metab.Home page
Y. Seval, H. Cakmak, U. A. Kayisli, and A. Arici
Estrogen-Mediated Regulation of p38 Mitogen-Activated Protein Kinase in Human Endometrium
J. Clin. Endocrinol. Metab., June 1, 2006; 91(6): 2349 - 2357.
[Abstract] [Full Text] [PDF]


Home page
Arterioscler. Thromb. Vasc. Bio.Home page
K. Niwano, M. Arai, N. Koitabashi, S. Hara, A. Watanabe, K. Sekiguchi, T. Tanaka, T. Iso, and M. Kurabayashi
Competitive Binding of CREB and ATF2 to cAMP/ATF Responsive Element Regulates eNOS Gene Expression in Endothelial Cells
Arterioscler. Thromb. Vasc. Biol., May 1, 2006; 26(5): 1036 - 1042.
[Abstract] [Full Text] [PDF]


Home page
J. Immunol.Home page
J. C. Hoyt, J. Ballering, H. Numanami, J. M. Hayden, and R. A. Robbins
Doxycycline Modulates Nitric Oxide Production in Murine Lung Epithelial Cells
J. Immunol., January 1, 2006; 176(1): 567 - 572.
[Abstract] [Full Text] [PDF]


Home page
Am. J. Physiol. Cell Physiol.Home page
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]


Home page
J. Biol. Chem.Home page
A. Thiefes, S. Wolter, J. F. Mushinski, E. Hoffmann, O. Dittrich-Breiholz, N. Graue, A. Dorrie, H. Schneider, D. Wirth, B. Luckow, et al.
Simultaneous Blockade of NF{kappa}B, JNK, and p38 MAPK by a Kinase-inactive Mutant of the Protein Kinase TAK1 Sensitizes Cells to Apoptosis and Affects a Distinct Spectrum of Tumor Necrosis Target Genes
J. Biol. Chem., July 29, 2005; 280(30): 27728 - 27741.
[Abstract] [Full Text] [PDF]


Home page
BloodHome page
J. Seybold, D. Thomas, M. Witzenrath, S. Boral, A. C. Hocke, A. Burger, A. Hatzelmann, H. Tenor, C. Schudt, M. Krull, et al.
Tumor necrosis factor-{alpha}-dependent expression of phosphodiesterase 2: role in endothelial hyperpermeability
Blood, May 1, 2005; 105(9): 3569 - 3576.
[Abstract] [Full Text] [PDF]


Home page
Int ImmunolHome page
S. Simoncini, C. Sapet, L. Camoin-Jau, N. Bardin, J.-R. Harle, J. Sampol, F. Dignat-George, and F. Anfosso
Role of reactive oxygen species and p38 MAPK in the induction of the pro-adhesive endothelial state mediated by IgG from patients with anti-phospholipid syndrome
Int. Immunol., April 1, 2005; 17(4): 489 - 500.
[Abstract] [Full Text] [PDF]


Home page
Am. J. Physiol. Heart Circ. Physiol.Home page
X.-L. Chen, J. Y. Grey, S. Thomas, F.-H. Qiu, R. M. Medford, M. A. Wasserman, and C. Kunsch
Sphingosine kinase-1 mediates TNF-{alpha}-induced MCP-1 gene expression in endothelial cells: upregulation by oscillatory flow
Am J Physiol Heart Circ Physiol, October 1, 2004; 287(4): H1452 - H1458.
[Abstract] [Full Text] [PDF]


Home page
J. Biol. Chem.Home page
W. J. Wurzer, C. Ehrhardt, S. Pleschka, F. Berberich-Siebelt, T. Wolff, H. Walczak, O. Planz, and S. Ludwig
NF-{kappa}B-dependent Induction of Tumor Necrosis Factor-related Apoptosis-inducing Ligand (TRAIL) and Fas/FasL Is Crucial for Efficient Influenza Virus Propagation
J. Biol. Chem., July 23, 2004; 279(30): 30931 - 30937.
[Abstract] [Full Text] [PDF]


Home page
Circ. Res.Home page
E. Suzuki, H. Satonaka, H. Nishimatsu, S. Oba, R. Takeda, M. Omata, T. Fujita, R. Nagai, and Y. Hirata
Myocyte Enhancer Factor 2 Mediates Vascular Inflammation via the p38-Dependent Pathway
Circ. Res., July 9, 2004; 95(1): 42 - 49.
[Abstract] [Full Text] [PDF]


Home page
J. Pharmacol. Exp. Ther.Home page
Y.-M. Chen, W.-C. Chiang, S.-L. Lin, K.-D. Wu, T.-J. Tsai, and B.-S. Hsieh
Dual Regulation of Tumor Necrosis Factor-{alpha}-Induced CCL2/Monocyte Chemoattractant Protein-1 Expression in Vascular Smooth Muscle Cells by Nuclear Factor-{kappa}B and Activator Protein-1: Modulation by Type III Phosphodiesterase Inhibition
J. Pharmacol. Exp. Ther., June 1, 2004; 309(3): 978 - 986.
[Abstract] [Full Text] [PDF]


Home page
BloodHome page
D. Viemann, M. Goebeler, S. Schmid, K. Klimmek, C. Sorg, S. Ludwig, and J. Roth
Transcriptional profiling of IKK2/NF-{kappa}B-- and p38 MAP kinasedependent gene expression in TNF-{alpha}--stimulated primary human endothelial cells
Blood, May 1, 2004; 103(9): 3365 - 3373.
[Abstract] [Full Text] [PDF]


Home page
J. Biol. Chem.Home page
B. Hou, M. Eren, C. A. Painter, J. W. Covington, J. D. Dixon, J. A. Schoenhard, and D. E. Vaughan
Tumor Necrosis Factor {alpha} Activates the Human Plasminogen Activator Inhibitor-1 Gene through a Distal Nuclear Factor {kappa}B Site
J. Biol. Chem., April 30, 2004; 279(18): 18127 - 18136.
[Abstract] [Full Text] [PDF]


Home page
Circ. Res.Home page
H. Satonaka, E. Suzuki, H. Nishimatsu, S. Oba, R. Takeda, A. Goto, M. Omata, T. Fujita, R. Nagai, and Y. Hirata
Calcineurin Promotes the Expression of Monocyte Chemoattractant Protein-1 in Vascular Myocytes and Mediates Vascular Inflammation
Circ. Res., March 19, 2004; 94(5): 693 - 700.
[Abstract] [Full Text] [PDF]


Home page
J. Immunol.Home page
W. Matsuyama, L. Wang, W. L. Farrar, M. Faure, and T. Yoshimura
Activation of Discoidin Domain Receptor 1 Isoform b with Collagen Up-Regulates Chemokine Production in Human Macrophages: Role of p38 Mitogen-Activated Protein Kinase and NF-{kappa}B
J. Immunol., February 15, 2004; 172(4): 2332 - 2340.
[Abstract] [Full Text] [PDF]


Home page
J. Biol. Chem.Home page
D. Baronas-Lowell, J. L. Lauer-Fields, and G. B. Fields
Induction of Endothelial Cell Activation by a Triple Helical {alpha}2{beta}1 Integrin Ligand, Derived from Type I Collagen {alpha}1(I)496-507
J. Biol. Chem., January 9, 2004; 279(2): 952 - 962.
[Abstract] [Full Text] [PDF]


Home page
Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
N. Gertzberg, P. Neumann, V. Rizzo, and A. Johnson
NAD(P)H oxidase mediates the endothelial barrier dysfunction induced by TNF-{alpha}
Am J Physiol Lung Cell Mol Physiol, January 1, 2004; 286(1): L37 - L48.
[Abstract] [Full Text] [PDF]


Home page
J. Pharmacol. Exp. Ther.Home page
M. Kawaguchi, F. Kokubu, S. Matsukura, K. Ieki, M. Odaka, S. Watanabe, S. Suzuki, M. Adachi, and S.-K. Huang
Induction of C-X-C Chemokines, Growth-Related Oncogene {alpha} Expression, and Epithelial Cell-Derived Neutrophil-Activating Protein-78 by ML-1 (Interleukin-17F) Involves Activation of Raf1-Mitogen-Activated Protein Kinase Kinase-Extracellular Signal-Regulated Kinase 1/2 Pathway
J. Pharmacol. Exp. Ther., December 1, 2003; 307(3): 1213 - 1220.
[Abstract] [Full Text] [PDF]


Home page
J. Am. Soc. Nephrol.Home page
R. Donadelli, C. Zanchi, M. Morigi, S. Buelli, C. Batani, S. Tomasoni, D. Corna, D. Rottoli, A. Benigni, M. Abbate, et al.
Protein Overload Induces Fractalkine Upregulation in Proximal Tubular Cells through Nuclear Factor {kappa}B- and p38 Mitogen-Activated Protein Kinase-Dependent Pathways
J. Am. Soc. Nephrol., October 1, 2003; 14(10): 2436 - 2446.
[Abstract] [Full Text] [PDF]


Home page
Am. J. Physiol. Renal Physiol.Home page
K. Takaya, D. Koya, M. Isono, T. Sugimoto, T. Sugaya, A. Kashiwagi, and M. Haneda
Involvement of ERK pathway in albumin-induced MCP-1 expression in mouse proximal tubular cells
Am J Physiol Renal Physiol, May 1, 2003; 284(5): F1037 - F1045.
[Abstract] [Full Text] [PDF]


Home page
Am. J. Physiol. Heart Circ. Physiol.Home page
J. Kaur, R. C. Woodman, and P. Kubes
P38 MAPK: critical molecule in thrombin-induced NF-kappa B-dependent leukocyte recruitment
Am J Physiol Heart Circ Physiol, April 1, 2003; 284(4): H1095 - H1103.
[Abstract] [Full Text] [PDF]


Home page
BloodHome page
C. Fiuza, M. Bustin, S. Talwar, M. Tropea, E. Gerstenberger, J. H. Shelhamer, and A. F. Suffredini
Inflammation-promoting activity of HMGB1 on human microvascular endothelial cells
Blood, April 1, 2003; 101(7): 2652 - 2660.
[Abstract] [Full Text] [PDF]


Home page
J. Am. Soc. Nephrol.Home page
Y. Iwata, T. Wada, K. Furuichi, N. Sakai, K. Matsushima, H. Yokoyama, and K.-i. Kobayashi
p38 Mitogen-Activated Protein Kinase Contributes to Autoimmune Renal Injury in MRL-Faslpr Mice
J. Am. Soc. Nephrol., January 1, 2003; 14(1): 57 - 67.
[Abstract] [Full Text] [PDF]


Home page
J. Immunol.Home page
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]


Home page
J. Am. Soc. Nephrol.Home page
T. Tanaka, T. Kuroiwa, H. Ikeuchi, F. Ota, Y. Kaneko, K. Ueki, Y. Tsukada, I. B. McInnes, D. T. Boumpas, and Y. Nojima
Human Platelets Stimulate Mesangial Cells to Produce Monocyte Chemoattractant Protein-1 via the CD40/CD40 Ligand Pathway and May Amplify Glomerular Injury
J. Am. Soc. Nephrol., October 1, 2002; 13(10): 2488 - 2496.
[Abstract] [Full Text] [PDF]


Home page
J. Biol. Chem.Home page
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]


Home page
Infect. Immun.Home page
N.-H. Cho, S.-Y. Seong, M.-S. Huh, N.-H. Kim, M.-s. Choi, and I.-s. Kim
Induction of the Gene Encoding Macrophage Chemoattractant Protein 1 by Orientia tsutsugamushi in Human Endothelial Cells Involves Activation of Transcription Factor Activator Protein 1
Infect. Immun., September 1, 2002; 70(9): 4841 - 4850.
[Abstract] [Full Text] [PDF]


Home page
J. Biol. Chem.Home page
M. Kawaguchi, L. F. Onuchic, and S.-K. Huang
Activation of Extracellular Signal-regulated Kinase (ERK)1/2, but Not p38 and c-Jun N-terminal Kinase, Is Involved in Signaling of a Novel Cytokine, ML-1
J. Biol. Chem., May 3, 2002; 277(18): 15229 - 15232.
[Abstract] [Full Text] [PDF]


Home page
Nephrol Dial TransplantHome page
K. Furuichi, T. Wada, Y. Iwata, N. Sakai, K. Yoshimoto, K.-i. Kobayashi, N. Mukaida, K. Matsushima, and H. Yokoyama
Administration of FR167653, a new anti-inflammatory compound, prevents renal ischaemia/reperfusion injury in mice
Nephrol. Dial. Transplant., March 1, 2002; 17(3): 399 - 407.
[Abstract] [Full Text] [PDF]


Home page
BloodHome page
V. Marin, C. Farnarier, S. Gres, S. Kaplanski, M. S.-S. Su, C. A. Dinarello, and G. Kaplanski
The p38 mitogen-activated protein kinase pathway plays a critical role in thrombin-induced endothelial chemokine production and leukocyte recruitment
Blood, August 1, 2001; 98(3): 667 - 673.
[Abstract] [Full Text] [PDF]


Home page
IOVSHome page
Z.-M. Bian, V. M. Elner, A. Yoshida, S. L. Kunkel, and S. G. Elner
Signaling Pathways for Glycated Human Serum Albumin-Induced IL-8 and MCP-1 Secretion in Human RPE Cells
Invest. Ophthalmol. Vis. Sci., June 1, 2001; 42(7): 1660 - 1668.
[Abstract] [Full Text]


Home page
Mol. Endocrinol.Home page
E. T. Maizels, A. Mukherjee, G. Sithanandam, C. A. Peters, J. Cottom, K. E. Mayo, and M. Hunzicker-Dunn
Developmental Regulation of Mitogen-Activated Protein Kinase-Activated Kinases-2 and -3 (MAPKAPK-2/-3) in Vivo during Corpus Luteum Formation in the Rat
Mol. Endocrinol., May 1, 2001; 15(5): 716 - 733.
[Abstract] [Full Text]