scholarly journals Induction of Host Matrix Metalloproteinases by Borrelia burgdorferi Differs in Human and Murine Lyme Arthritis

2005 ◽  
Vol 73 (1) ◽  
pp. 126-134 ◽  
Author(s):  
Aruna K. Behera ◽  
Ethan Hildebrand ◽  
Joanna Scagliotti ◽  
Allen C. Steere ◽  
Linden T. Hu

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.

2020 ◽  
Vol 15 (1) ◽  
pp. 971-980
Author(s):  
Shicheng Zheng ◽  
Jing Ren ◽  
Sihai Gong ◽  
Feng Qiao ◽  
Jinlong He

AbstractC1q/TNF-related protein 9 (CTRP9), the closest paralog of adiponectin, has been reported to protect against inflammation-related diseases. However, its role in regulating osteoarthritis (OA) has not been fully elucidated. First, a rat model of OA was generated. Furthermore, rats with OA were injected with different doses of recombinant CTRP9 protein (rCTRP9), and the knee cartilage damage was evaluated. Finally, the phosphorylation of p38 and the secretion of matrix metalloproteinases (MMPs) were detected by Western blotting and enzyme-linked immunosorbent assay. Results revealed that CTRP9 was highly expressed in adipose tissue, followed by skeletal muscle and cartilage tissue, and less expressed in liver, kidney and lung. Moreover, the expression of CTRP9 significantly decreased in the monosodium iodoacetate (MIA) group in the knee cartilage and knee synovial fluid, and the contents of interleukin-1β (IL-1β) and IL-6 significantly increased in knee synovial fluid. In addition, rCTRP9 alleviated MIA-induced inflammation, oxidative stress and knee cartilage damage in a dose-dependent way. In addition, rCTRP9 could attenuate the expression of p38MAPK and p-p38 and suppress the expression of nuclear factor-kappa B (NF-κB), p65 and MMPs. Collectively, the results of the present study suggested that CTRP9 alleviates the inflammation of MIA-induced OA through deactivating p38MAPK and NF-κB signaling pathways in rats.


2007 ◽  
Vol 205 (1) ◽  
pp. 133-141 ◽  
Author(s):  
Utpal Pal ◽  
Penghua Wang ◽  
Fukai Bao ◽  
Xiuli Yang ◽  
Swapna Samanta ◽  
...  

Lyme arthritis results from colonization of joints by Borrelia burgdorferi and the ensuing host response. Using gene array–based differential analysis of B. burgdorferi gene expression and quantitative reverse trancription-polymerase chain reaction, we identified two paralogous spirochete genes, bmpA and bmpB, that are preferentially up-regulated in mouse joints compared with other organs. Transfer of affinity-purified antibodies against either BmpA or BmpB into B. burgdorferi–infected mice selectively reduced spirochete numbers and inflammation in the joints. B. burgdorferi lacking bmpA/B were therefore generated to further explore the role of these proteins in the pathogenesis of Lyme disease. B. burgdorferi lacking bmpA/B were infectious in mice, but unable to persist in the joints, and they failed to induce severe arthritis. Complementation of the mutant spirochetes with a wild-type copy of the bmpA and bmpB genes partially restored the original phenotype. These data delineate a role for differentially produced B. burgdorferi antigens in spirochete colonization of mouse joints, and suggest new strategies for the treatment of Lyme arthritis.


2001 ◽  
Vol 184 (2) ◽  
pp. 174-180 ◽  
Author(s):  
Bo Lin ◽  
J. Michael Kidder ◽  
Richard Noring ◽  
Allen C. Steere ◽  
Mark S. Klempner ◽  
...  

1994 ◽  
Vol 330 (4) ◽  
pp. 229-234 ◽  
Author(s):  
James J. Nocton ◽  
Frank Dressler ◽  
Barbara J. Rutledge ◽  
Paul N. Rys ◽  
David H. Persing ◽  
...  

2012 ◽  
Vol 19 (11) ◽  
pp. 1806-1809 ◽  
Author(s):  
Sam S. Barclay ◽  
Michael T. Melia ◽  
Paul G. Auwaerter

ABSTRACTThe primary objective of this study was to determine whether patients with putative late-onset Lyme arthritis based upon synovial fluidBorrelia burgdorferiIgM and IgG immunoblot testing offered by commercial laboratories satisfied conventional criteria for the diagnosis of Lyme arthritis. Secondary objectives included assessing the prior duration and responsiveness of associated antibiotic therapy. We conducted a retrospective analysis of 11 patients referred to an academic medical center infectious disease clinic during the years 2007 to 2009 with a diagnosis of Lyme disease based upon previously obtained synovial fluidB. burgdorferiimmunoblot testing. Ten of the 11 (91%) patients with a diagnosis of late-onset Lyme arthritis based upon interpretation of synovial fluidB. burgdorferiimmunoblot testing were seronegative and did not satisfy published criteria for the diagnosis of late-onset Lyme arthritis. None of the 10 patients had a clinical response to previously received antibiotics despite an average course of 72 days. Diagnosis of Lyme arthritis should not be based on synovial fluidB. burgdorferiimmunoblot testing. This unvalidated test does not appear useful for the diagnosis of Lyme disease, and this study reinforces the longstanding recommendation to useB. burgdorferiimmunoblot testing only on serum samples and not other body fluids. Erroneous interpretations of “positive” synovial fluid immunoblots may lead to inappropriate antibiotic courses and delays in diagnosis of other joint diseases.


1994 ◽  
Vol 169 (3) ◽  
pp. 668-672 ◽  
Author(s):  
D. H. Persing ◽  
B. J. Rutledge ◽  
P. N. Rys ◽  
D. S. Podzorski ◽  
P. D. Mitchell ◽  
...  

Sign in / Sign up

Export Citation Format

Share Document