| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
,
*
Department of Human Genetics, National Institute of Genetics, Yata, Mishima, Shizuoka; and
First Department of Internal Medicine and
Department of Clinical Chemistry and Laboratory Medicine, Faculty of Medicine, Kyushu University, Maidashi, Higashi-ku, Fukuoka, Japan
LPS is a potent stimulator of monocytes, inducing many of their
functions. Although the details of how LPS exerts such functions remain
largely unknown, transcription factors such as nuclear factor-
B,
nuclear factor-IL-6, and activator protein-1 have been shown to be
involved in this process. However, to date it has been thought that no
known STAT molecule plays a role in the activation of monocytes by LPS.
In this study we examined whether some known STAT molecule is
stimulated by LPS, based on the finding that a GAS motif sequence is
conserved in the promoter regions of human, mouse, and rat
cyclo-oxygenase-2 (COX-2) genes. Consequently, LPS induced activation
of STAT5 in human monocytes, and this STAT5 activation occurred in an
indirect way via granulocyte-macrophage CSF (GM-CSF) secreted by
LPS-stimulated monocytes. Expression of COX-2 protein was partially
reduced by treatment of anti-human GM-CSF Ab. Activation of STAT5
was inhibited by either IL-10 or dexamethasone (Dex), but not by
aspirin. IL-10 blocked activation of STAT5 indirectly by suppressing
GM-CSF production, while Dex inhibited this activation both directly
and indirectly. Taken together, these results suggest that in addition
to other transcription factors, STAT5 plays an important role in
activation of monocytes by LPS, and that STAT5 is another target for
IL-10 and Dex to inhibit COX-2 expression in activated monocytes.
This article has been cited by other articles:
|
|
 |
|
  H.-W. Koon, D. Zhao, Y. Zhan, S. H. Rhee, M. P. Moyer, and C. Pothoulakis Substance P Stimulates Cyclooxygenase-2 and Prostaglandin E2 Expression through JAK-STAT Activation in Human Colonic Epithelial Cells. J. Immunol., April 15, 2006; 176(8): 5050 - 5059. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Mouihate, S. Ellis, E.-M. Harre, and Q. J. Pittman Fever suppression in near-term pregnant rats is dissociated from LPS-activated signaling pathways Am J Physiol Regulatory Integrative Comp Physiol, November 1, 2005; 289(5): R1265 - R1272. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Kim, S. H. Rhee, E. Kokkotou, X. Na, T. Savidge, M. P. Moyer, C. Pothoulakis, and J. T. LaMont Clostridium difficile Toxin A Regulates Inducible Cyclooxygenase-2 and Prostaglandin E2 Synthesis in Colonocytes via Reactive Oxygen Species and Activation of p38 MAPK J. Biol. Chem., June 3, 2005; 280(22): 21237 - 21245. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Matsuda, K. Ferreri, I. Todorov, Y. Kuroda, C. V. Smith, F. Kandeel, and Y. Mullen Silymarin Protects Pancreatic {beta}-Cells against Cytokine-Mediated Toxicity: Implication of c-Jun NH2-Terminal Kinase and Janus Kinase/Signal Transducer and Activator of Transcription Pathways Endocrinology, January 1, 2005; 146(1): 175 - 185. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Severgnini, S. Takahashi, L. M. Rozo, R. J. Homer, C. Kuhn, J. W. Jhung, G. Perides, M. Steer, P. M. Hassoun, B. L. Fanburg, et al. Activation of the STAT pathway in acute lung injury Am J Physiol Lung Cell Mol Physiol, June 1, 2004; 286(6): L1282 - L1292. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Inoue, T. Otsuka, H. Niiro, S. Nagano, Y. Arinobu, E. Ogami, M. Akahoshi, K. Miyake, I. Ninomiya, S. Shimizu, et al. Novel Regulatory Mechanisms of CD40-Induced Prostanoid Synthesis by IL-4 and IL-10 in Human Monocytes J. Immunol., February 15, 2004; 172(4): 2147 - 2154. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. S. Kang, M. J. Lee, H. Song, S. H. Han, Y. M. Kim, J. Y. Im, and I. Choi Molecular Identification of IgE-Dependent Histamine-Releasing Factor as a B Cell Growth Factor J. Immunol., June 1, 2001; 166(11): 6545 - 6554. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Ohmori and T. A. Hamilton Requirement for STAT1 in LPS-induced gene expression in macrophages J. Leukoc. Biol., April 1, 2001; 69(4): 598 - 604. [Abstract] [Full Text]
|
|
|
|
|
|
D. S. Whittaker, K. S. Bahjat, L. L. Moldawer, and M. J. Clare-Salzler Autoregulation of Human Monocyte-Derived Dendritic Cell Maturation and IL-12 Production by Cyclooxygenase- 2-Mediated Prostanoid Production J. Immunol., October 15, 2000; 165(8): 4298 - 4304. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Mutoh, M. Takahashi, K. Fukuda, Y. Matsushima-Hibiya, H. Mutoh, T. Sugimura, and K. Wakabayashi Suppression of cyclooxygenase-2 promoter-dependent transcriptional activity in colon cancer cells by chemopreventive agents with a resorcin-type structure Carcinogenesis, May 1, 2000; 21(5): 959 - 963. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Barrios-Rodiles, G. Tiraloche, and K. Chadee Lipopolysaccharide Modulates Cyclooxygenase-2 Transcriptionally and Posttranscriptionally in Human Macrophages Independently from Endogenous IL-1{beta} and TNF-{alpha} J. Immunol., July 15, 1999; 163(2): 963 - 969. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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]
|
|
|
|
|
|
P. Delerive, P. Gervois, J.-C. Fruchart, and B. Staels Induction of Ikappa Balpha Expression as a Mechanism Contributing to the Anti-inflammatory Activities of Peroxisome Proliferator-activated Receptor-alpha Activators J. Biol. Chem., November 17, 2000; 275(47): 36703 - 36707. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
