| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
*
Department of Medicine, Northwestern University Medical School, Chicago, IL 60611;
Institute of Medical Science, University of Tokyo, Tokyo, Japan; and
Department of Veterans’Affairs, Chicago Health Care System, Lakeside Division, Chicago, IL 60611
The rheumatoid arthritis (RA) joint is characterized by an
inflammatory synovial pannus which mediates tissue destruction. IL-13
is a cytokine that inhibits activated monocytes/macrophages from
secreting a variety of proinflammatory molecules. The aim of this study
was to examine whether gene therapy-delivered IL-13 could reduce the
production of key proinflammatory mediators in RA synovial tissue (ST)
explants. Adenoviral vectors encoding the genes for human IL-13
(AxCAIL-13) and bacterial ß-galactosidase were generated and examined
for protein production. Vectors were used to infect RA ST explants and
RA synovial fibroblasts, and conditioned medium (CM) was collected at
various times for analysis by ELISA and competitive immunoassay.
AxCAIL-13 decreased the production of RA ST explant proinflammatory
IL-1ß by 85% after 24 h. Likewise, TNF-
levels were
decreased by 82 and 75% whereas IL-8 levels were reduced 54 and 82%
after 24 and 48 h, respectively, in RA ST explant CM. Monocyte
chemotactic protein-1 concentrations were decreased by 88% after
72 h in RA ST explant CM. RA ST explant epithelial
neutrophil-activating peptide-78 concentrations were decreased 85 and
94% whereas growth-related gene product- levels were decreased by
77 and 85% at 24 and 48 h, respectively, by AxCAIL-13. Further,
IL-13 significantly decreased PGE2 and macrophage
inflammatory protein-1 production. These results demonstrate that
increased expression of IL-13 via gene therapy may decrease
RA-associated inflammation by reducing secretion of proinflammatory
cytokines and PGE2.
This article has been cited by other articles:
|
|
 |
|
  D. Cihakova, J. G. Barin, M. Afanasyeva, M. Kimura, D. Fairweather, M. Berg, M. V. Talor, G. C. Baldeviano, S. Frisancho, K. Gabrielson, et al. Interleukin-13 Protects Against Experimental Autoimmune Myocarditis by Regulating Macrophage Differentiation Am. J. Pathol., May 1, 2008; 172(5): 1195 - 1208. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. Gonsiorek, X. Fan, D. Hesk, J. Fossetta, H. Qiu, J. Jakway, M. Billah, M. Dwyer, J. Chao, G. Deno, et al. Pharmacological Characterization of Sch527123, a Potent Allosteric CXCR1/CXCR2 Antagonist J. Pharmacol. Exp. Ther., August 1, 2007; 322(2): 477 - 485. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. M. Black, J. F. Grehan, A. L. Rivard, B. A. Benson, A. E. Wahner, A. E. Koch, B. K. Levay-Young, and A. P. Dalmasso Porcine Endothelial Cells and Iliac Arteries Transduced with AdenoIL-4 Are Intrinsically Protected, through Akt Activation, against Immediate Injury Caused by Human Complement J. Immunol., November 15, 2006; 177(10): 7355 - 7363. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. W. Hipkin, G. Deno, J. Fine, Y. Sun, B. Wilburn, X. Fan, W. Gonsiorek, and M. T. Wiekowski Cloning and Pharmacological Characterization of CXCR1 and CXCR2 from Macaca fascicularis J. Pharmacol. Exp. Ther., July 1, 2004; 310(1): 291 - 300. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. E. Kolodsick, G. B. Toews, C. Jakubzick, C. Hogaboam, T. A. Moore, A. McKenzie, C. A. Wilke, C. J. Chrisman, and B. B. Moore Protection from Fluorescein Isothiocyanate-Induced Fibrosis in IL-13-Deficient, but Not IL-4-Deficient, Mice Results from Impaired Collagen Synthesis by Fibroblasts J. Immunol., April 1, 2004; 172(7): 4068 - 4076. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
