Co-culture of human fibroblasts and Borrelia burgdorferi enhances collagen and growth factor mRNA

Abstract

Skin fibrosis has been reported in Borrelia burgdorferi infection in Europe, but has been questioned by several authors. The objective of the present study was to examine the interaction of skin fibroblasts with B. burgdorferi sensu stricto B31 (BB) and B. afzelii (BA) in vitro by electron microscopy. We also determined the expression of collagen type I, TGF-β, FGF-1, calreticulin (CALR), decorin (DCN), and PDGF-α at the mRNA level in Borrelia/fibroblast co-cultures. Intact Borrelia attach to and transmigrate fibroblasts, and undergo cystic transformation outside the fibroblasts. Fibroblasts preserve their vitality and express a prominent granular endoplasmic reticulum, suggesting activated protein synthesis. On two different semi-quantitative real-time PCR assays, BB- and BA/fibroblast co-cultures showed a significant induction of type I collagen mRNA after 2 days compared to fibroblasts (fourfold for BA and 1.8-fold for BB; p < 0.02). In addition, there was a significant upregulation of mRNA expression of TGF-β, CALR, PDGF-α, and DCN in BA and BB co-cultures compared to control fibroblasts in monolayer cultures after 2 days (p < 0.01). The BA/fibroblast co-culture induced a considerably greater upregulation of collagen and growth factor mRNA compared to BB/fibroblast co-culture. In contrast, a significant down-regulation of FGF-1 (20-fold for BA and 4.5-fold for BB) mRNA expression was detected in co-cultures compared to controls (p < 0.01). The results of the study support the hypothesis that BB sensu lato, and BA in particular, enhances collagen mRNA expression and can stimulate growth factors responsible for increased collagen production.

Successful treatment with oral minocycline in a case with a long‐standing idiopathic atrophoderma of Pasini and Pierini: Histopathological comparison with the contralateral normal skin

“…2 Recent evidence that fibroblasts co-cultured with Borrelia species overexpressed collagen-1a and growth factors support the causative link between Borrelia infection and skin fibrosis. 3 Notwithstanding the favorable responsiveness to systemic antibiotics, 2 it remains unclear as to whether long-standing and/or juvenile-onset IAPP, like our case, carry the preceding infection with Borrelia or other antibiotic-responsive species. Together with the unlikely infection episode in most IAPP…”

“…2 Dermal fibrosclerosis identified on histopathological examination is associated with a higher risk of refractory fibrosis in children. 3 These findings show that early diagnosis and prompt and appropriate treatment are necessary to prevent permanent cutaneous sclerosis, particularly in children.…”

Effect of Invasion of Borrelia burgdorferi in Normal and Neoplastic Mammary Epithelial Cells

“…Other in vitro studies have also demonstrated the internalization of B. burgdorferi in various mammalian cells. For example, co-culturing human skin fibroblasts cells with B. burgdorferi at a MOI of 1000 showed B. burgdorferi binding to the fibroblast membrane after 24 h and invaginating within the fibroblast’s cytoplasm within 48 h [ 27 ]. B. burgdorferi spirochetes have been shown to attach to human synovial cells (SCs) along with partial or complete internalization into the cells after 90 min [ 28 ].…”

Scoping review and interpretation of Myofascial Pain/Fibromyalgia syndrome: an attempt to assemble a medical puzzle

“…Borrelia and fibroblast co-cultures show a significant induction of type I collagen mRNA after 2 days (p < 0·02) and a significant upregulation of mRNA expression of TGF-β (p < 0·01). 180 Since TGF-β is a cardinal signal for myofibroblast α-SMA synthesis this may explain why, of all infections, Lyme disease (and not viral encephalitis or infective transverse myelitis) is strongly associated with fibromyalgia. Biopsy studies of fibromyalgia patients find that in fibroblasts, TGF-ß gene expression is significantly higher in fibromyalgia patients compared to controls (p < 0·001).…”