Lyme disease is a multisystemic disorder caused by the spirochete Borrelia burgdorferi. One major clinical manifestation of the disease is chronic arthritis. The molecular mechanisms of how B. burgdorferi induces arthritis is not understood. Recently, we have identified several high molecular mass collagenase activities in B. burgdorferi (Grab et al., FEMS Microbiol). Letters 144 39) which we speculate play a major role in the disease process. We now report that B. burgdorferi is also able to degrade proteoglycans and induce nitric oxide (NO) production by articular cartilage in an in vitro system. The degradation of cartilage proteoglycan appears to proceed via a cytokine-independent mechanism. The proteoglycanase activity is not attributable to bound plasmin(ogen) since it was insensitive to aprotinin, indicating that the enzyme(s) are an inherent component (collagenase?) of the spirochete. Tetracyclines are common antibiotics used to treat Lyme disease. Since tetracycline (i.e. doxycycline) is also known to inhibit some collagenase(s) and proteoglycanse(s) it was of interest to determine if B. burgdorferi collagense/ proteoglycanase(s) activities could also be blocked by this antibiotic. Preliminary studies thus far indicate that doxycycline has little effect on the spirochete enzymes. In addition to proteoglycan degradation, we also found that B. burgdorferi lysates can induce NO release from articular cartilage in a cytokine-dependent manner. NO stimulation by a mutant strain of borrelia lacking OspA and OspB suggests that other Osp proteins also have the ability to induce NO. Seiler et al. (Infect. Immun. 63 3886) found that B. burgdorferi are resistant to NO and that NO does not play a role in the induction of Lyme arthritis. We propose that spirochete associated proteoglycanases and collagenases play a direct role in cartilage destruction while NO may impede mechanisms of cartilage repair.
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