| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
in Human Monocytic Cells: Distinct Involvement of c-Jun N-Terminal Kinase in LPS-Induced CD44 Expression
,,
Departments of
* Pediatrics, and
Biochemistry, Microbiology and Immunology, University of Ottawa, and
Division of Virology and Molecular Immunology, Research Institute, Children’s Hospital of Eastern Ontario, Ottawa, Ontario, Canada;
Division of Infectious Diseases, Department of Medicine, Vancouver Hospital, University of British Columbia, Vancouver, British Columbia, Canada; and
¶ Therapeutic Products Program, Research Services Division, Health Canada, Ottawa, Ontario, Canada
Alterations in the regulation of CD44 expression play a critical
role in modulating cell adhesion, migration, and inflammation. LPS, a
bacterial cell wall component, regulates CD44 expression and may
modulate CD44-mediated biological effects in monocytic cells during
inflammation and immune responses. In this study, we show that in
normal human monocytes, LPS and LPS-induced cytokines IL-10 and TNF-
enhance CD44 expression. To delineate the mechanism underlying
LPS-induced CD44 expression, we investigated the role of the
mitogen-activated protein kinases (MAPKs), p38, p42/44 extracellular
signal-regulated kinase, and c-Jun N-terminal kinase (JNK) by using
their specific inhibitors. We demonstrate the involvement, at least in
part, of p38 MAPK in TNF--induced CD44 expression in both monocytes
and promonocytic THP-1 cells. However, neither p38 nor p42/44 MAPKs
were involved in IL-10-induced CD44 expression in monocytes. To further
dissect the TNF- and LPS-induced signaling pathways regulating CD44
expression independent of IL-10-mediated effects, we used IL-10
refractory THP-1 cells as a model system. Herein, we show that CD44
expression induced by the LPS-mediated pathway predominantly involved
JNK activation. This conclusion was based on results derived by
transfection of THP-1 cells with a dominant-negative mutant of
stress-activated protein/extracellular signal-regulated kinase kinase
1, and by exposure of cells to JNK inhibitors dexamethasone and
SP600125. All these treatments prevented CD44 induction
in LPS-stimulated, but not in TNF--stimulated, THP-1 cells.
Furthermore, we show that CD44 induction may involve JNK-dependent
early growth response gene activation in LPS-stimulated monocytic
cells. Taken together, these results suggest a predominant role of JNK
in LPS-induced CD44 expression in monocytic
cells.
This article has been cited by other articles:
|
|
 |
|
  E. Vachon, R. Martin, V. Kwok, V. Cherepanov, C.-W. Chow, C. M. Doerschuk, J. Plumb, S. Grinstein, and G. P. Downey CD44-mediated phagocytosis induces inside-out activation of complement receptor-3 in murine macrophages Blood, December 15, 2007; 110(13): 4492 - 4502. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Zoller, P. Gupta, R. Marhaba, M. Vitacolonna, and P. Freyschmidt-Paul Anti-CD44-mediated blockade of leukocyte migration in skin-associated immune diseases J. Leukoc. Biol., July 1, 2007; 82(1): 57 - 71. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Muthukumaran, K. E. Miletti-Gonzalez, A. K. Ravindranath, and L. Rodriguez-Rodriguez Tumor Necrosis Factor-{alpha} Differentially Modulates CD44 Expression in Ovarian Cancer Cells Mol. Cancer Res., August 1, 2006; 4(8): 511 - 520. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. P. Mishra, S. Mishra, K. Gee, and A. Kumar Differential Involvement of Calmodulin-dependent Protein Kinase II-activated AP-1 and c-Jun N-terminal Kinase-activated EGR-1 Signaling Pathways in Tumor Necrosis Factor-{alpha} and Lipopolysaccharide-induced CD44 Expression in Human Monocytic Cells J. Biol. Chem., July 22, 2005; 280(29): 26825 - 26837. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. A. R. Rahimi, K. Gee, S. Mishra, W. Lim, and A. Kumar STAT-1 Mediates the Stimulatory Effect of IL-10 on CD14 Expression in Human Monocytic Cells J. Immunol., June 15, 2005; 174(12): 7823 - 7832. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. CHEN, Q. KE, Y. YANG, J. S. RANA, J. TANG, J. P. MORGAN, and Y.-F. XIAO Cardiomyocytes overexpressing TNF-{alpha} attract migration of embryonic stem cells via activation of p38 and c-Jun amino-terminal kinase FASEB J, December 1, 2003; 17(15): 2231 - 2239. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Joiakim, P. A. Mathieu, C. Palermo, T. A. Gasiewicz, and J. J. Reiners Jr. THE JUN N-TERMINAL KINASE INHIBITOR SP600125 IS A LIGAND AND ANTAGONIST OF THE ARYL HYDROCARBON RECEPTOR Drug Metab. Dispos., November 1, 2003; 31(11): 1279 - 1282. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Gee, M. Kozlowski, and A. Kumar Tumor Necrosis Factor-{alpha} Induces Functionally Active Hyaluronan-adhesive CD44 by Activating Sialidase through p38 Mitogen-activated Protein Kinase in Lipopolysaccharide-stimulated Human Monocytic Cells J. Biol. Chem., September 26, 2003; 278(39): 37275 - 37287. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
