Matrix Metalloproteinase 9 Plays a Key Role in Lyme Arthritis but Not in Dissemination ofBorrelia burgdorferi

Abstract

Borrelia burgdorferi, the causative agent of Lyme arthritis, does not produce any exported proteases capable of degrading extracellular matrix despite the fact that it is able to disseminate from a skin insertion site to infect multiple organs. Prior studies have shown that B. burgdorferi induces the host protease, matrix metalloproteinase 9 (MMP-9), and suggested that the induction of MMP-9 may allow the organism to disseminate and produce local tissue destruction. We examined the role of MMP-9 in dissemination of B. burgdorferi and pathogenesis of Lyme arthritis. In a MMP-9؊/؊ mouse model, MMP-9 was not required for the dissemination of the spirochete to distant sites. However, MMP-9 ؊/؊ exhibited significantly decreased arthritis compared to wild-type mice. The decrease in arthritis was not due to an inability to control infection since the spirochete numbers in the joints were identical. Levels of inflammatory chemokines and cytokines were also similar in MMP-9 ؊/؊ and wild-type mice. We examined whether decreased inflammation in MMP-9 ؊/؊ mice may be the result of decreased production of neoattractants by MMP-9-dependent cleavage of collagen. MMP-9 cleavage of type I collagen results in increased monocyte chemoattraction. MMP-9 plays an important role in regulating inflammation in Lyme arthritis, potentially through the cleavage of type I collagen.

Expression levels and association of gelatinases MMP-2 and MMP-9 and collagenases MMP-1 and MMP-13 with VEGF in synovial fluid of patients with arthritis

“…Thus, total MMP-9 level may be a useful indicator for differentiating between RA and OA. To support the relevance of MMP-9 in angiogenesis, MMP-9 gene knockout mice are significantly less susceptible to arthritis [15,16]. In contrast with the results of other studies, in our study, total MMP-2 levels did not seem to be involved in angiogenesis in either RA or OA pannus, judging from their relationship with total MMP-2 and VEGF.…”

Interleukin-10 Alters Effector Functions of Multiple Genes Induced by Borrelia burgdorferi in Macrophages To Regulate Lyme Disease Inflammation

“…MMP9 is also upregulated in erythema migrans lesions of Lyme disease patients (99,100) and in joints of Lyme diseasesusceptible mice (7). Recent studies by Heilpern et al (46) using MMP9 knockout mice infected with B. burgdorferi revealed reduced arthritis in these animals, suggesting that MMP9 plays a role in the genesis of this form of Lyme disease. In the present study, B. burgdorferi-induced MMP9 was downregulated 2-fold in the presence of IL-10, using TaqMan assays, indicating the ability of this cytokine to target select genes that contribute to the overall B. burgdorferi-induced inflammation.…”

The role of iNOS in cholesterol-induced liver fibrosis

“…MMP-9 may have a role in modulation of inflammation through proteolytic activation of proinflammatory cytokines/chemokines including IL-1β, TGF-β, and membrane-bound TNFα. [56][57][58] The relationship between iNOS-induced NO and MMP-9 induction is highly complex and has received much attention in the last two decades. 59 Under inflammatory conditions there is a concurrent upregulation of both iNOS and MMP-9.…”