| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
* Pulmonary and Critical Care Medicine, Brigham and Women’s Hospital, Boston, MA 02115; Harvard Medical School, Boston, MA 02115;
Division of Infectious Diseases, Department of Internal Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
Heme oxygenase-1 (HO-1) is a cytoprotective enzyme that is acutely induced by inflammatory stimuli, and the products of HO-1-mediated heme degradation have anti-inflammatory properties. In many different pathophysiologic states, the up-regulation of HO-1 has been shown to be beneficial in combating the detrimental consequences of increased inflammation. Ets transcription factors are known to be important mediators of inflammatory responses, and the ternary complex factor subfamily of Ets proteins has both transcriptional activation and repression activity. The present study demonstrates that of several ternary complex factor subfamily members, only Elk-3 represses HO-1 promoter activity in macrophages. Endotoxin administration to macrophages led to a dose-dependent decrease in endogenous Elk-3 mRNA levels, and this reduction in Elk-3 preceded the LPS-mediated up-regulation of HO-1 message. Analogous results also occurred in lung tissue of mice exposed to endotoxin. Two putative Ets binding sites (EBS1 and EBS2) are present in the downstream region of the murine HO-1 promoter (bp –125 and –93, respectively), and we recently showed that the EBS2 site is essential for HO-1 induction by endotoxin. In contrast, the present study demonstrates that the repressive effect of Elk-3 on HO-1 promoter activity is dependent on the EBS1 site. Taken together, our data reveal that Elk-3 serves as an important repressor of HO-1 gene transcription and contributes to the tight control of HO-1 gene regulation in the setting of inflammatory stimuli.
This article has been cited by other articles:
|
|
 |
|
  L. E. Fredenburgh, O. D. Liang, A. A. Macias, T. R. Polte, X. Liu, D. F. Riascos, S. W. Chung, S. L. Schissel, D. E. Ingber, S. A. Mitsialis, et al. Absence of Cyclooxygenase-2 Exacerbates Hypoxia-Induced Pulmonary Hypertension and Enhances Contractility of Vascular Smooth Muscle Cells Circulation, April 22, 2008; 117(16): 2114 - 2122. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. Olive, N. Wagner, S. Chan, P. Kastner, C. Vannetti, F. Cuzin, and M. Rassoulzadegan PU.1 (Sfpi1), a pleiotropic regulator expressed from the first embryonic stages with a crucial function in germinal progenitors Development, November 1, 2007; 134(21): 3815 - 3825. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Gross, G. Buchwalter, H. Dubois-Pot, E. Cler, H. Zheng, and B. Wasylyk The Ternary Complex Factor Net Is Downregulated by Hypoxia and Regulates Hypoxia-Responsive Genes Mol. Cell. Biol., June 1, 2007; 27(11): 4133 - 4141. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Oettgen Regulation of Vascular Inflammation and Remodeling by ETS Factors Circ. Res., November 24, 2006; 99(11): 1159 - 1166. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
