Submitted on August 1, 2002
Accepted on January 7, 2003
Robust induction of PGHS-2 by IL-1 in orbital fibroblasts results from low levels of IL-1 receptor antagonist expression
H. James Cao1, Rui Han2, and Terry J Smith3*
1 Molecular and Cellular Medicine and Samuel S. Stratton Veterans Affairs Medical Center, Albany Medical College, Albany, NY, USA
2 Division of Molecular Medicine and the David Geffen School of Medicine at UCLA, Harbor-UCLA Medical Center, Torrance, CA, USA; Molecular and Cellular Medicine and Samuel S. Stratton Veterans Affairs Medical Center, Albany Medical College, Albany, NY, USA
3 Division of Molecular Medicine and the David Geffen School of Medicine at UCLA, Harbor-UCLA Medical Center, Torrance, CA, USA; Long Beach Veterans Affairs Medical Center, Long Beach, CA, USA; Molecular and Cellular Medicine and Samuel S. Stratton Veterans Affairs Medical Center, Albany Medical College, Albany, NY, USA
* To whom correspondence should be addressed. E-mail: tjsmith{at}ucla.edu.
Human orbital fibroblasts are more susceptible to some actions of pro-inflammatory cytokines than are fibroblasts from other anatomic regions. These cells produce high levels of PGE2 when activated by cytokines. Here we report that they express high levels of PGHS-2, the inflammatory cyclooxygenase, when treated with IL-1
. This induction results from enhanced PGHS-2 mRNA stability and small increases in gene promoter activity. The enhanced transcript stabilty is a result of actions of the cytokine on the 3' untranslated region. Orbital fibroblasts, unlike those from skin, fail to express high levels of IL-1 receptor antagonist (IL-1ra)when treated with IL-1, leading to loss of modulation of IL-1 action. This can be overcome by transiently transfecting cells with IL-1ra. Thus, a decreased level of IL-1ra expression in orbital fibroblasts may underlie the exaggerated responses to IL-1 observed in those cells and therefore the susceptibility of the orbit to inflammation.
