| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
,
* Department of Microbiology and Infectious Diseases, Faculty of Medicine, University of Calgary, Calgary, Alberta, Canada;
Department of Laboratory Medicine and Pathobiology and Department of Immunology, University of Toronto, Toronto, Ontario, Canada;
Department of Pathology and Rosalind Franklin Comprehensive Diabetes Center, Chicago Medical School, North Chicago, IL 60064; and
Department of Biochemistry, Chosun University School of Medicine, Seosuk-Dong, Gwangju, Korea
Macrophages are activated during an inflammatory response and produce multiple inflammatory cytokines. IL-18 is one of the most important innate cytokines produced from macrophages in the early stages of the inflammatory immune response. Monocyte chemoattractant protein (MCP-1) is expressed in many inflammatory diseases such as multiple sclerosis and rheumatoid arthritis, and its expression is correlated with the severity of the disease. Both IL-18 and MCP-1 have been shown to be involved in inflammatory immune responses. However, it has been unclear whether IL-18 is involved in the induction of MCP-1. This investigation was initiated to determine whether IL-18 can induce MCP-1 production, and if so, by which signal transduction pathways. We found that IL-18 induced the production of MCP-1 in macrophages, which was IL-12-independent and was not mediated by autocrine cytokines such as IFN-
or TNF-
. We then examined signal transduction pathways involved in IL-18-induced MCP-1 production. We found that IL-18 did not activate the I
B kinase/NF-B pathway, evidenced by no degradation of IB and no translocation of NF-B p65 to the nucleus in IL-18-stimulated macrophages. Instead, IL-18 activated the PI3K/Akt and MEK/ERK1/2 pathways. Inhibition of either of these pathways attenuated MCP-1 production in macrophages, and inhibition of both signaling pathways resulted in the complete inhibition of MCP-1 production. On the basis of these observations, we conclude that IL-18 induces MCP-1 production through the PI3K/Akt and MEK/ERK1/2 pathways in macrophages.
This article has been cited by other articles:
|
|
 |
|
  J. Sun, R. D. Ramnath, R. Tamizhselvi, and M. Bhatia Role of protein kinase C and phosphoinositide 3-kinase-Akt in substance P-induced proinflammatory pathways in mouse macrophages FASEB J, April 1, 2009; 23(4): 997 - 1010. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Z. He, L. Lu, C. Altmann, T. S. Hoke, D. Ljubanovic, A. Jani, C. A. Dinarello, S. Faubel, and C. L. Edelstein Interleukin-18 binding protein transgenic mice are protected against ischemic acute kidney injury Am J Physiol Renal Physiol, November 1, 2008; 295(5): F1414 - F1421. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. P. Carroll, V. Paunovic, and M. Gadina Signalling, inflammation and arthritis: Crossed signals: the role of interleukin-15 and -18 in autoimmunity Rheumatology, September 1, 2008; 47(9): 1269 - 1277. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Z. Sameermahmood, M. Balasubramanyam, T. Saravanan, and M. Rema Curcumin Modulates SDF-1{alpha}/CXCR4-Induced Migration of Human Retinal Endothelial Cells (HRECs) Invest. Ophthalmol. Vis. Sci., August 1, 2008; 49(8): 3305 - 3311. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. L. Stern and B. Slobedman Human Cytomegalovirus Latent Infection of Myeloid Cells Directs Monocyte Migration by Up-Regulating Monocyte Chemotactic Protein-1 J. Immunol., May 15, 2008; 180(10): 6577 - 6585. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Chan, E. R. Bivins-Smith, M. S. Smith, and A. D. Yurochko Transcriptome Analysis of NF-{kappa}B- and Phosphatidylinositol 3-Kinase-Regulated Genes in Human Cytomegalovirus-Infected Monocytes J. Virol., January 15, 2008; 82(2): 1040 - 1046. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. H. Nazarian, M. M. Rahman, S. J. Werden, D. Villeneuve, X. Meng, C. Brunetti, C. Valeriano, C. Wong, R. Singh, J. W. Barrett, et al. Yaba Monkey Tumor Virus Encodes a Functional Inhibitor of Interleukin-18 J. Virol., January 1, 2008; 82(1): 522 - 528. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S.-M. Dai, Z.-Z. Shan, H. Xu, and K. Nishioka Cellular targets of interleukin-18 in rheumatoid arthritis Ann Rheum Dis, November 1, 2007; 66(11): 1411 - 1418. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
