Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Subscribe

Logo for

J. Biol. Chem. 276 (19): 16555-16560

© 2001 by The American Society for Biochemistry and Molecular Biology, Inc.

Distinct Signaling Pathways for MCP-1-dependent Integrin Activation and Chemotaxis*

Noboru Ashida, Hidenori AraiDagger , Masahide Yamasaki, and Toru Kita

From the Department of Geriatric Medicine, Kyoto University Graduate School of Medicine, Kyoto, 606-8507, Japan

Transmigration of monocytes to the subendothelial space is the initial step of atherosclerotic plaque formation and inflammation. Integrin activation and chemotaxis are two important functions involved in monocyte transmigration. To delineate the signaling cascades leading to integrin activation and chemotaxis by monocyte chemoattractant protein-1 (MCP-1), we have investigated the roles of MAPK and Rho GTPases in THP-1 cells, a monocytic cell line. MCP-1 stimulated beta 1 integrin-dependent, but not beta 2 integrin-dependent cell adhesion in a time-dependent manner. MCP-1-mediated cell adhesion was inhibited by a MEK inhibitor but not by a p38-MAPK inhibitor. In contrast, MCP-1-mediated chemotaxis was inhibited by the p38-MAPK inhibitor but not by the MEK inhibitor. The inhibitor of Rho GTPase, C3 exoenzyme, and a Rho kinase inhibitor abrogated MCP-1-dependent chemotaxis but not integrin-dependent cell adhesion. Further, C3 exoenzyme and the Rho kinase inhibitor blocked MCP-1-dependent p38-MAPK activation. These data indicate that ERK is responsible for integrin activation, that p38-MAPK and Rho are responsible for chemotaxis mediated by MCP-1, and that Rho and the Rho kinase are upstream of p38-MAPK in MCP-1-mediated signaling. This study demonstrates that two distinct MAPKs regulate two dependent signaling cascades leading to integrin activation and chemotaxis induced by MCP-1 in THP-1 cells.


* This study was supported by grants-in-aid from the Ministry of Education, Science, Sports, and Culture of Japan; International Scientific Research Program grants from the Japanese Ministry of Education, Science, Sports, and Culture; Center of Excellence grants from the Japanese Ministry of Education, Science, Sports, and Culture; and a research grant for health sciences from the Japanese Ministry of Health and Welfare.The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Dagger To whom the correspondence should be addressed: Dept. of Geriatric Medicine, Kyoto University Graduate School of Medicine, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan. Tel.: 81-75-751-3463; Fax: 81-75-751-3463; E-mail: harai@kuhp.kyoto-u.ac.jp.


Copyright © 2001 by The American Society for Biochemistry and Molecular Biology, Inc.

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
CCL2 Shapes Macrophage Polarization by GM-CSF and M-CSF: Identification of CCL2/CCR2-Dependent Gene Expression Profile.
E. Sierra-Filardi, C. Nieto, A. Dominguez-Soto, R. Barroso, P. Sanchez-Mateos, A. Puig-Kroger, M. Lopez-Bravo, J. Joven, C. Ardavin, J. L. Rodriguez-Fernandez, et al. (2014)
J. Immunol. 192, 3858-3867
   Abstract »    Full Text »    PDF »
A Circadian Clock Gene, Rev-erb{alpha}, Modulates the Inflammatory Function of Macrophages through the Negative Regulation of Ccl2 Expression.
S. Sato, T. Sakurai, J. Ogasawara, M. Takahashi, T. Izawa, K. Imaizumi, N. Taniguchi, H. Ohno, and T. Kizaki (2014)
J. Immunol. 192, 407-417
   Abstract »    Full Text »    PDF »
Redox regulation of MAPK phosphatase 1 controls monocyte migration and macrophage recruitment.
H. S. Kim, S. L. Ullevig, D. Zamora, C. F. Lee, and R. Asmis (2012)
PNAS 109, E2803-E2812
   Abstract »    Full Text »    PDF »
p38 Mitogen-activated Protein Kinase (MAPK) Promotes Cholesterol Ester Accumulation in Macrophages through Inhibition of Macroautophagy.
S. Mei, H. Gu, A. Ward, X. Yang, H. Guo, K. He, Z. Liu, and W. Cao (2012)
J. Biol. Chem. 287, 11761-11768
   Abstract »    Full Text »    PDF »
Macrophage Migration Inhibitory Factor and CD74 Regulate Macrophage Chemotactic Responses via MAPK and Rho GTPase.
H. Fan, P. Hall, L. L. Santos, J. L. Gregory, G. Fingerle-Rowson, R. Bucala, E. F. Morand, and M. J. Hickey (2011)
J. Immunol. 186, 4915-4924
   Abstract »    Full Text »    PDF »
MCP-1/CCR2B-dependent loop upregulates MUC5AC and MUC5B in human airway epithelium.
M. E. Monzon, R. M. Forteza, and S. M. Casalino-Matsuda (2011)
Am J Physiol Lung Cell Mol Physiol 300, L204-L215
   Abstract »    Full Text »    PDF »
Galectin-1 stimulates monocyte chemotaxis via the p44/42 MAP kinase pathway and a pertussis toxin-sensitive pathway.
R. K J Malik, R. R Ghurye, D. J Lawrence-Watt, and H. J S Stewart (2009)
Glycobiology 19, 1402-1407
   Abstract »    Full Text »    PDF »
Tumor Necrosis Factor-{alpha} Potentiates RhoA-Mediated Monocyte Transmigratory Activity In Vivo at a Picomolar Level.
S. Lim, J. Ryu, J.-A. Shin, M.-J. Shin, Y. K. Ahn, J. J. Kim, and K. H. Han (2009)
Arterioscler Thromb Vasc Biol 29, 2138-2145
   Abstract »    Full Text »    PDF »
Angiotensin II enhances the increase in monocyte chemoattractant protein-1 production induced by tumor necrosis factor-{alpha} from 3T3-L1 preadipocytes.
S. Asamizu, M. Urakaze, C. Kobashi, M. Ishiki, A. K. Norel Din, S. Fujisaka, Y. Kanatani, A. Bukahari, S. Senda, H. Suzuki, et al. (2009)
J. Endocrinol. 202, 199-205
   Abstract »    Full Text »    PDF »
Phosphatidylcholine hydroperoxide-induced THP-1 cell adhesion to intracellular adhesion molecule-1.
A. Asai, F. Okajima, K. Nakagawa, D. Ibusuki, K. Tanimura, Y. Nakajima, M. Nagao, M. Sudo, T. Harada, T. Miyazawa, et al. (2009)
J. Lipid Res. 50, 957-965
   Abstract »    Full Text »    PDF »
Deficiency of ROCK1 in bone marrow-derived cells protects against atherosclerosis in LDLR-/- mice.
H.-W. Wang, P.-Y. Liu, N. Oyama, Y. Rikitake, S. Kitamoto, J. Gitlin, J. K. Liao, and W. A. Boisvert (2008)
FASEB J 22, 3561-3570
   Abstract »    Full Text »    PDF »
Synergy between Coproduced CC and CXC Chemokines in Monocyte Chemotaxis through Receptor-Mediated Events.
M. Gouwy, S. Struyf, S. Noppen, E. Schutyser, J.-Y. Springael, M. Parmentier, P. Proost, and J. Van Damme (2008)
Mol. Pharmacol. 74, 485-495
   Abstract »    Full Text »    PDF »
CB2 cannabinoid receptor agonist JWH-015 modulates human monocyte migration through defined intracellular signaling pathways.
F. Montecucco, F. Burger, F. Mach, and S. Steffens (2008)
Am J Physiol Heart Circ Physiol 294, H1145-H1155
   Abstract »    Full Text »    PDF »
Gene variants of monocyte chemoattractant protein 1 and components of metabolic syndrome in KORA S4, Augsburg.
E.-M. Sedlmeier, H. Grallert, C. Huth, H. Lowel, C. Herder, K. Strassburger, G. Giani, H-E. Wichmann, H. Hauner, T. Illig, et al. (2007)
Eur. J. Endocrinol. 156, 377-385
   Abstract »    Full Text »    PDF »
Monocyte chemoattractant protein 1 mediates retinal detachment-induced photoreceptor apoptosis.
T. Nakazawa, T. Hisatomi, C. Nakazawa, K. Noda, K. Maruyama, H. She, A. Matsubara, S. Miyahara, S. Nakao, Y. Yin, et al. (2007)
PNAS 104, 2425-2430
   Abstract »    Full Text »    PDF »
PSGL-1 and mTOR regulate translation of ROCK-1 and physiological functions of macrophages.
R. Fox, T. Q. Nhan, G. L. Law, D. R. Morris, W. C. Liles, and S. M. Schwartz (2007)
EMBO J. 26, 505-515
   Abstract »    Full Text »    PDF »
Epac1-Rap1 signaling regulates monocyte adhesion and chemotaxis.
M. J. Lorenowicz, J. van Gils, M. de Boer, P. L. Hordijk, and M. Fernandez-Borja (2006)
J. Leukoc. Biol. 80, 1542-1552
   Abstract »    Full Text »    PDF »
Overexpression of Monocyte Chemoattractant Protein-1 in Adipose Tissues Causes Macrophage Recruitment and Insulin Resistance.
N. Kamei, K. Tobe, R. Suzuki, M. Ohsugi, T. Watanabe, N. Kubota, N. Ohtsuka-Kowatari, K. Kumagai, K. Sakamoto, M. Kobayashi, et al. (2006)
J. Biol. Chem. 281, 26602-26614
   Abstract »    Full Text »    PDF »
The CC Chemokine MCP-1 Stimulates Surface Expression of CX3CR1 and Enhances the Adhesion of Monocytes to Fractalkine/CX3CL1 via p38 MAPK.
S. R. Green, K. H. Han, Y. Chen, F. Almazan, I. F. Charo, Y. I. Miller, and O. Quehenberger (2006)
J. Immunol. 176, 7412-7420
   Abstract »    Full Text »    PDF »
Rho-mediated regulation of tight junctions during monocyte migration across the blood-brain barrier in HIV-1 encephalitis (HIVE).
Y. Persidsky, D. Heilman, J. Haorah, M. Zelivyanskaya, R. Persidsky, G. A. Weber, H. Shimokawa, K. Kaibuchi, and T. Ikezu (2006)
Blood 107, 4770-4780
   Abstract »    Full Text »    PDF »
The {gamma}-Parvin-Integrin-Linked Kinase Complex Is Critically Involved in Leukocyte-Substrate Interaction.
R. Yoshimi, S. Yamaji, A. Suzuki, W. Mishima, M. Okamura, T. Obana, C. Matsuda, Y. Miwa, S. Ohno, and Y. Ishigatsubo (2006)
J. Immunol. 176, 3611-3624
   Abstract »    Full Text »    PDF »
MAPKAPK-2-mediated LIM-kinase activation is critical for VEGF-induced actin remodeling and cell migration.
M. Kobayashi, M. Nishita, T. Mishima, K. Ohashi, and K. Mizuno (2006)
EMBO J. 25, 713-726
   Abstract »    Full Text »    PDF »
G Protein-coupled Receptor Kinase 2 Negatively Regulates Chemokine Signaling at a Level Downstream from G Protein Subunits.
M. C. Jimenez-Sainz, C. Murga, A. Kavelaars, M. Jurado-Pueyo, B. F. Krakstad, C. J. Heijnen, F. Mayor Jr., and A. M. Aragay (2006)
Mol. Biol. Cell 17, 25-31
   Abstract »    Full Text »    PDF »
GRO family chemokines are specialized for monocyte arrest from flow.
D. F. Smith, E. Galkina, K. Ley, and Y. Huo (2005)
Am J Physiol Heart Circ Physiol 289, H1976-H1984
   Abstract »    Full Text »    PDF »
Discovery and Pharmacological Characterization of a Novel Rodent-Active CCR2 Antagonist, INCB3344.
C. M. Brodmerkel, R. Huber, M. Covington, S. Diamond, L. Hall, R. Collins, L. Leffet, K. Gallagher, P. Feldman, P. Collier, et al. (2005)
J. Immunol. 175, 5370-5378
   Abstract »    Full Text »    PDF »
Specific CXC but not CC chemokines cause elevated monocyte migration in COPD: a role for CXCR2.
S. L. Traves, S. J. Smith, P. J. Barnes, and L. E. Donnelly (2004)
J. Leukoc. Biol. 76, 441-450
   Abstract »    Full Text »    PDF »
The soluble D2D388-274 fragment of the urokinase receptor inhibits monocyte chemotaxis and integrin-dependent cell adhesion.
F. Furlan, S. Orlando, C. Laudanna, M. Resnati, V. Basso, F. Blasi, and A. Mondino (2004)
J. Cell Sci. 117, 2909-2916
   Abstract »    Full Text »    PDF »
Upregulation of SR-PSOX/CXCL16 and Recruitment of CD8+ T Cells in Cardiac Valves During Inflammatory Valvular Heart Disease.
R. Yamauchi, M. Tanaka, N. Kume, M. Minami, T. Kawamoto, K. Togi, T. Shimaoka, S. Takahashi, J. Yamaguchi, T. Nishina, et al. (2004)
Arterioscler Thromb Vasc Biol 24, 282-287
   Abstract »    Full Text »    PDF »
Soluble Fractalkine Prevents Monocyte Chemoattractant Protein-1-Induced Monocyte Migration via Inhibition of Stress-Activated Protein Kinase 2/p38 and Matrix Metalloproteinase Activities.
S. Vitale, A. Schmid-Alliana, V. Breuil, M. Pomeranz, M.-A. Millet, B. Rossi, and H. Schmid-Antomarchi (2004)
J. Immunol. 172, 585-592
   Abstract »    Full Text »    PDF »
Long-Term Inhibition of Rho-Kinase Suppresses Neointimal Formation After Stent Implantation in Porcine Coronary Arteries: Involvement of Multiple Mechanisms.
Y. Matsumoto, T. Uwatoku, K. Oi, K. Abe, T. Hattori, K. Morishige, Y. Eto, Y. Fukumoto, K.-i. Nakamura, Y. Shibata, et al. (2004)
Arterioscler Thromb Vasc Biol 24, 181-186
   Abstract »    Full Text »    PDF »
T cell aggregation induced through CD43: intracellular signals and inhibition by the immunomodulatory drug leflunomide.
E. Layseca-Espinosa, G. Pedraza-Alva, J. L. Montiel, R. del Rio, N. A. Fierro, R. Gonzalez-Amaro, and Y. Rosenstein (2003)
J. Leukoc. Biol. 74, 1083-1093
   Abstract »    Full Text »
Matrix Metalloproteinase-9 Silencing by RNA Interference Triggers the Migratory-adhesive Switch in Ewing's Sarcoma Cells.
J. Sanceau, S. Truchet, and B. Bauvois (2003)
J. Biol. Chem. 278, 36537-36546
   Abstract »    Full Text »    PDF »
Opposing Roles of Ras/Raf Oncogenes and the MEK1/ERK Signaling Module in Regulation of Expression and Adhesive Function of Surface Transglutaminase.
S. S. Akimov and A. M. Belkin (2003)
J. Biol. Chem. 278, 35609-35619
   Abstract »    Full Text »    PDF »
Signaling Pathways for Monocyte Chemoattractant Protein 1-Mediated Extracellular Signal-Regulated Kinase Activation.
M. C. Jimenez-Sainz, B. Fast, F. Mayor Jr., and A. M. Aragay (2003)
Mol. Pharmacol. 64, 773-782
   Abstract »    Full Text »    PDF »
2-Arachidonoylglycerol Induces the Migration of HL-60 Cells Differentiated into Macrophage-like Cells and Human Peripheral Blood Monocytes through the Cannabinoid CB2 Receptor-dependent Mechanism.
S. Kishimoto, M. Gokoh, S. Oka, M. Muramatsu, T. Kajiwara, K. Waku, and T. Sugiura (2003)
J. Biol. Chem. 278, 24469-24475
   Abstract »    Full Text »    PDF »
RhoA and ROCK Promote Migration by Limiting Membrane Protrusions.
R. A. Worthylake and K. Burridge (2003)
J. Biol. Chem. 278, 13578-13584
   Abstract »    Full Text »    PDF »
Vortex-mediated Mechanical Stress Induces Integrin-dependent Cell Adhesion Mediated by Inositol 1,4,5-Trisphosphate-sensitive Ca2+ Release in THP-1 Cells.
N. Ashida, H. Takechi, T. Kita, and H. Arai (2003)
J. Biol. Chem. 278, 9327-9331
   Abstract »    Full Text »    PDF »
The chemokine receptor CCR8 mediates rescue from dexamethasone-induced apoptosis via an ERK-dependent pathway.
G. Spinetti, G. Bernardini, G. Camarda, A. Mangoni, A. Santoni, M. C. Capogrossi, and M. Napolitano (2003)
J. Leukoc. Biol. 73, 201-207
   Abstract »    Full Text »    PDF »
beta -Arrestin2 Is Critically Involved in CXCR4-mediated Chemotaxis, and This Is Mediated by Its Enhancement of p38 MAPK Activation.
Y. Sun, Z. Cheng, L. Ma, and G. Pei (2002)
J. Biol. Chem. 277, 49212-49219
   Abstract »    Full Text »    PDF »
The Serine Protease Plasmin Triggers Expression of MCP-1 and CD40 in Human Primary Monocytes via Activation of p38 MAPK and Janus Kinase (JAK)/STAT Signaling Pathways.
L. Burysek, T. Syrovets, and T. Simmet (2002)
J. Biol. Chem. 277, 33509-33517
   Abstract »    Full Text »    PDF »
Mechanosensitive Transcription Factors Involved in Endothelin B Receptor Expression.
M. Cattaruzza, I. Eberhardt, and M. Hecker (2001)
J. Biol. Chem. 276, 36999-37003
   Abstract »    Full Text »    PDF »

To Advertise     Find Products


Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882