BorreliaSpirochetes Upregulate Release and Activation of Matrix Metalloproteinase Gelatinase B (MMP-9) and Collagenase 1 (MMP-1) in Human Cells

Abstract

Borrelia burgdorferi, the spirochetal agent of Lyme disease, stimulated human peripheral blood monocytes to release pro-matrix metalloproteinase-9 (gelatinase B; pro-MMP-9) and active matrix metalloproteinase-1 (collagenase-1; MMP-1). Human neutrophils also released pro-MMP-9 and a 130-kDa protein with gelatinolytic activity in response to live B. burgdorferi. In addition, U937 cells and human keratinocyte cells were also stimulated to release pro-MMP-9 under the same conditions. However, human umbilical vein endothelial cells (HUVECs) released pro-MMP-9 and pro-MMP-2 in a constitutive manner and were not influenced by live spirochetes. MMPs produced by human monocytes also enhanced the penetration of B. burgdorferi through extracellular matrix component barriers in vitro. Plasmin stabilized on the surface of the Lyme disease spirochete was shown to activate pro-MMP-9 to its active form. This active form was also observed in the plasma of mice infected with a relapsing fever borrelia. These results suggest that borreliae can upregulate MMPs and possibly mediate an activation cascade initiated by plasmin bound to the microbial surface. MMPs may play a role in dissemination of the Lyme disease spirochete and in the pathogenesis of Borrelia infection.

Gene Expression Profiling Reveals Unique Pathways Associated with Differential Severity of Lyme Arthritis

“…Microarray revealed modest increases in gene products associated with chondrocytes from the joints of 4 wk postinfection C3H mice, including several collagen genes, such as Ctsk and Dspg3 (Table V) In agreement with findings reported by others (42,43), transcripts for Mmp3, Mmp9, Mmp13, and Mmp23, as well as tissue inhibitor of matrix metalloproteinase 1 (Timp1) were induced in the joints of C3H mice, whereas transcripts for Mmp3, Mmp8, and Timp1 were increased in C57BL/6-IL-10 Ϫ/Ϫ mice (Table V). Mmp3 expression was also increased in joints of C57BL/6 mice, but to a lesser extent than in C3H or C57BL/6-IL-10 Ϫ/Ϫ mice.…”

Delayed Invasion of the Kidney and Brain byBorrelia crociduraein Plasminogen-Deficient Mice

“…Binding of Plg to the surface of bacteria has been proposed to be of importance for the invasion capacity of a number of pathogenic bacterial species belonging to several genera, including Borrelia (13,16,22). So far, in vivo studies of the role of Plg binding in pathogenicity have been performed for few organisms.…”

Expression profiling, gene silencing and transcriptional networking of metzincin metalloproteases in the cattle tick, Rhipicephalus (Boophilus) microplus

“…It has also been speculated that such metzincins may play a role in pathogen transmission, since it has been proven that Borrelia spirochetes up regulate the release and activation of matrix metalloprotease gelatinase B (MMP-9) and collagenase 1 (MMP-1) in human cells, improving the transmission of Borrelia burgdorferi across extracellular matrix components (Gebbia et al, 2001). Spirochete dissemination through vertebrate tissues may similarly be aided by salivary metalloproteases and other salivary anti-haemostatic agents (Maritz-Olivier et al, 2007;Ribeiro, 1989), which prevent fibrin clot formation and dissolution of the fibrin clots eventually formed around the feeding cavity of ixodid ticks (Francischetti et al, 2003).…”