| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
1From the Cooperative Research Centre for Eye Research and Technology and Cornea and Contact Lens Research Unit, School of Optometry and Vision Science, and 2Inflammation Research Unit, School of Medical Sciences, Department of Pathology, The University of New South Wales, Sydney, New South Wales, Australia.
PURPOSE. This study was conducted to investigate the role of IL-1ß in the regulation of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) in a mouse model of experimental keratitis and corneal injury.
METHODS. Mice were injected subconjunctivally with 10 µg of anti-mouse IL-1ß antibody 2 hours before challenge with Pseudomonas aeruginosa (strain 6294). Control animals received an equal volume and concentration of isotype control antibody at the same time. Eyes were enucleated at 0, 8, 24, and 72 hours, after bacterial challenge and processed for histologic examination. Some eyes were homogenized and used to evaluate production of MMP-2, MMP-9, TIMP-1, and TIMP-2 protein, by zymography and reverse zymography.
RESULTS. Injury without bacterial infection resulted in increases in both MMP-2 and -9 and a slight but significant downregulation of TIMP-1. Administration of anti-IL-1ß just before injury and without bacterial infection resulted in a significant reduction in expression of MMP-2 (at 8 hours), MMP-9 (at 8 hours), TIMP-1 (at 8 and 72 hours), and TIMP-2 (at 8 hours). Mice treated with anti-IL-1ß antibody, before bacterial challenge, demonstrated markedly reduced corneal damage compared with the severe corneal injury and massive neutrophil infiltration observed in infected mice treated with control antibody. Administration of the neutralizing anti-IL-1ß antibody resulted in a significant reduction of MMP-9 and a change in the time course of TIMP-1 and -2 expression. The reduction in MMP-9 by anti-IL-1ß during infection was much greater than the reduction without infection.
CONCLUSIONS. The results imply that IL-1ß has a central role in corneal destruction during bacterial keratitis and suggests that targeting IL-1ß may be a novel therapeutic strategy for microbial keratitis.
This article has been cited by other articles:
|
|
 |
|
  X. Yuan, B. M. Mitchell, and K. R. Wilhelmus Expression of Matrix Metalloproteinases during Experimental Candida albicans Keratitis Invest. Ophthalmol. Vis. Sci., February 1, 2009; 50(2): 737 - 742. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Karicherla and J. A. Hobden Nona-D-Arginine Therapy for Pseudomonas aeruginosa Keratitis Invest. Ophthalmol. Vis. Sci., January 1, 2009; 50(1): 256 - 262. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Ng, M. T. Coroneo, D. Wakefield, and N. Di Girolamo Ultraviolet Radiation and the Role of Matrix Metalloproteinases in the Pathogenesis of Ocular Surface Squamous Neoplasia Invest. Ophthalmol. Vis. Sci., December 1, 2008; 49(12): 5295 - 5306. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Lin, P. Jackson, A. M. Tester, E. Diaconu, C. M. Overall, J. E. Blalock, and E. Pearlman Matrix Metalloproteinase-8 Facilitates Neutrophil Migration through the Corneal Stromal Matrix by Collagen Degradation and Production of the Chemotactic Peptide Pro-Gly-Pro Am. J. Pathol., July 1, 2008; 173(1): 144 - 153. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. B. H. Hume, N. Cole, L. L. Garthwaite, S. Khan, and M. D. P. Willcox A Protective Role for IL-6 in Staphylococcal Microbial Keratitis Invest. Ophthalmol. Vis. Sci., November 1, 2006; 47(11): 4926 - 4930. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Fukuda, Y. Fujitsu, N. Kumagai, and T. Nishida Inhibition of matrix metalloproteinase-3 synthesis in human conjunctival fibroblasts by interleukin-4 or interleukin-13. Invest. Ophthalmol. Vis. Sci., July 1, 2006; 47(7): 2857 - 2864. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. J. Burton, R. J. C. Bowman, H. Faal, E. A. N. Aryee, U. N. Ikumapayi, N. D. E. Alexander, R. A. Adegbola, D. C. W. Mabey, A. Foster, G. J. Johnson, et al. The long-term natural history of trachomatous trichiasis in the gambia. Invest. Ophthalmol. Vis. Sci., March 1, 2006; 47(3): 847 - 852. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. A. McClellan, X. Huang, R. P. Barrett, S. Lighvani, Y. Zhang, D. Richiert, and L. D. Hazlett Matrix Metalloproteinase-9 Amplifies the Immune Response to Pseudomonas aeruginosa Corneal Infection Invest. Ophthalmol. Vis. Sci., January 1, 2006; 47(1): 256 - 264. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 X. Zhou, F. Li, L. Kong, H. Tomita, C. Li, and W. Cao Involvement of Inflammation, Degradation, and Apoptosis in a Mouse Model of Glaucoma J. Biol. Chem., September 2, 2005; 280(35): 31240 - 31248. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. M. Lee, B.-J. Yoon, K. Osiewicz, M. Preston, B. Bundy, A. M. van Heeckeren, Z. Werb, and P. D. Soloway Tissue Inhibitor of Metalloproteinase 1 Regulates Resistance to Infection Infect. Immun., January 1, 2005; 73(1): 661 - 665. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. J. Burton, R. L. Bailey, D. Jeffries, D. C. W. Mabey, and M. J. Holland Cytokine and Fibrogenic Gene Expression in the Conjunctivas of Subjects from a Gambian Community Where Trachoma Is Endemic Infect. Immun., December 1, 2004; 72(12): 7352 - 7356. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Thakur, R. P. Barrett, J. A. Hobden, and L. D. Hazlett Caspase-1 Inhibitor Reduces Severity of Pseudomonas aeruginosa Keratitis in Mice Invest. Ophthalmol. Vis. Sci., September 1, 2004; 45(9): 3177 - 3184. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. M. Stuart, F. Pan, X. Yin, Z. Haskova, S. Plambeck, and T. A. Ferguson Effect of Metalloprotease Inhibitors on Corneal Allograft Survival Invest. Ophthalmol. Vis. Sci., April 1, 2004; 45(4): 1169 - 1173. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
