Affiliation:
1. Department of Infectious Disease, Tupper Research Institute, New England Medical Center, Tufts University School of Medicine
2. Center for Immunology and Inflammatory Diseases, Division of Rheumatology, Allergy and Immunology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts
Abstract
ABSTRACT
Matrix metalloproteinases (MMPs) are induced from host tissues in response to
Borrelia burgdorferi
. Upregulation of MMPs may play a role in the dissemination of the organism through extracellular matrix tissues, but it can also result in destructive pathology. Although mice are a well-accepted model for Lyme arthritis, there are significant differences compared to human disease. We sought to determine whether MMP expression could account for some of these differences. MMP expression patterns following
B. burgdorferi
infection were analyzed in primary human chondrocytes, synovial fluid samples from patients with Lyme arthritis, and cartilage tissue from Lyme arthritis-susceptible and -resistant mice by using a gene array, real-time PCR, an enzyme-linked immunosorbent assay, and immunohistochemistry.
B. burgdorferi
infection significantly induced transcription of MMP-1, -3, -13, and -19 from primary human chondrocyte cells. Transcription of MMP-10 and tissue inhibitor of metalloprotease 1 was increased with
B. burgdorferi
infection, but protein expression was only minimally increased. The synovial fluid levels of MMPs from patients with high and low spirochete burdens were consistent with results seen in the in vitro studies.
B. burgdorferi
-susceptible C3H/HeN mice infected with
B. burgdorferi
showed induction of MMP-3 and MMP-19 but no other MMP or tissue inhibitor of metalloprotease. As determined by immunohistochemistry, MMP-3 expression was increased only in chondrocytes near the articular surface. The levels of MMPs were significantly lower in the more Lyme arthritis-resistant BALB/c and C57BL/6 mice. Differences between human and murine Lyme arthritis may be related to the lack of induction of collagenases, such MMP-1 and MMP-13, in mouse joints.
Publisher
American Society for Microbiology
Subject
Infectious Diseases,Immunology,Microbiology,Parasitology
Reference50 articles.
1. Ahrens, D., A. E. Koch, R. M. Pope, M. Stein-Picarella, and M. J. Niedbala. 1996. Expression of matrix metalloproteinase 9 (96-kd gelatinase B) in human rheumatoid arthritis. Arthritis Rheum.39:1576-1587.
2. Anonymous. 1995. Recommendations for test performance and interpretation from the Second National Conference on Serologic Diagnosis of Lyme Disease. Morb. Mortal. Wkly. Rep.44:590-591.
3. Baker, A. H., D. R. Edwards, and G. Murphy. 2002. Metalloproteinase inhibitors: biological actions and therapeutic opportunities. J. Cell Sci.115:3719-3727.
4. Balbin, M., A. Fueyo, V. Knauper, J. M. Lopez, J. Alvarez, L. M. Sanchez, V. Quesada, J. Bordallo, G. Murphy, and C. Lopez-Otin. 2001. Identification and enzymatic characterization of two diverging murine counterparts of human interstitial collagenase (MMP-1) expressed at sites of embryo implantation. J. Biol. Chem.276:10253-10262.
5. Barbour, A. 1984. Isolation and cultivation of Lyme disease spirochetes. Yale J. Biol. Med.57:521-525.
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