| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1 Department of Pulmonary and Critical Care Medicine, Cleveland Clinic, Cleveland, Ohio, USA; Department of Cancer Biology, Cleveland Clinic, Cleveland, Ohio, USA
2 Department of Virology, Cleveland Clinic, Cleveland, Ohio, USA
3 Department of Cancer Biology, Cleveland Clinic, Cleveland, Ohio, USA; Department of Pulmonary and Critical Care Medicine, Cleveland Clinic, Cleveland, Ohio, USA
* To whom correspondence should be addressed. E-mail: erzurus{at}ccf.org.
Cystic fibrosis (CF) airway epithelial cells are more susceptible to viral infection due to impairment of the innate host defense pathway of nitric oxide (NO). NO synthase 2 (NOS2) expression is absent, and signal transducer and activator of transcription (STAT) 1 activation is reduced in CF. We hypothesized that the IFN-
signaling pathway which leads to NOS2 gene induction in CF airway epithelial cells is defective. In contrast to lack of NOS2 induction, the major histocompatibility complex, class 2 (MHCII), an IFN-
regulated delayed-responsive gene is similarly induced in CF and non-CF airway epithelial cells (NL), suggesting a NOS2 specific defect in the IFN- signaling pathway. STAT1 and activator protein 1 (AP-1), both required for NOS2 gene expression, interact
normally in CF cells. Protein inhibitor of activated STAT1 (PIAS1) is not increased in CF cells. Interferon- induces NOS2 expression in airway epithelial cells through an autocrine mechanism involving synthesis and secretion of IFN--inducible mediator(s), which activates STAT1. Here, CF cells secrete IFN- inducible factor(s) which stimulate NOS2 expression in NL cells, but not in CF cells. In contrast, IFN- inducible factor(s)
similarly inhibit virus in CF and NL cells. Thus, autocrine activation of NOS2 is defective in CF cells, but IFN- induction of antiviral host defense is intact.
This article has been cited by other articles:
|
|
 |
|
  M. E. Manson, D. A. Corey, N. M. White, and T. J. Kelley cAMP-mediated regulation of cholesterol accumulation in cystic fibrosis and Niemann-Pick type C cells Am J Physiol Lung Cell Mol Physiol, November 1, 2008; 295(5): L809 - L819. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Grasemann, F. Ratjen, D. Schnabel, E. Reutershahn, U. Vester, and H. Grasemann Effect of growth hormone therapy on nitric oxide formation in cystic fibrosis patients Eur. Respir. J., April 1, 2008; 31(4): 815 - 821. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. M. Wright, C. A. Merlo, J. B. Reynolds, P. L. Zeitlin, J. G. N. Garcia, W. B. Guggino, and M. P. Boyle Respiratory Epithelial Gene Expression in Patients with Mild and Severe Cystic Fibrosis Lung Disease Am. J. Respir. Cell Mol. Biol., September 1, 2006; 35(3): 327 - 336. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A Moeller, F Horak Jr, C Lane, D Knight, A Kicic, S Brennan, P Franklin, J Terpolilli, J H Wildhaber, and S M Stick Inducible NO synthase expression is low in airway epithelium from young children with cystic fibrosis Thorax, June 1, 2006; 61(6): 514 - 520. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Grasemann, R. Schwiertz, S. Matthiesen, K. Racke, and F. Ratjen Increased Arginase Activity in Cystic Fibrosis Airways Am. J. Respir. Crit. Care Med., December 15, 2005; 172(12): 1523 - 1528. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| Visit Other APS Journals Online |
