Schwann cells producing matrix metalloproteinases under Mycobacterium leprae stimulation may play a role in the outcome of leprous neuropathy.
Matrix metalloproteinases (MMPs) mediate demyelination and breakdown of the blood-nerve barrier in peripheral neuropathies. Matrix metalloproteinases and tissue inhibitor of metalloproteinase 1 gene expression and secretion were studied in cells of the human Schwann cell line ST88-14 stimulated with Mycobacterium leprae and tumor necrosis factor (TNF) and in nerve biopsies from patients with neural leprosy (n = 21) and nonleprous controls (n = 3). Mycobacterium leprae and TNF induced upregulation of MMP-2 and MMP-9 and increased secretion of these enzymes in cultured ST88-14 cells. The effects of TNF and M. leprae were synergistic, and anti-TNF antibody blockage partially inhibited this synergistic effect. Nerves with inflammatory infiltrates and fibrosis displayed higher TNF, MMP-2, and MMP-9 mRNA than controls. Leprous nerve biopsies with no inflammatory alterations also exhibited higher MMP-2 and MMP-9; tissue inhibitor of metalloproteinase 1 was significantly higher in biopsies with fibrosis and inflammation. Immunohistochemical double labeling of the nerves demonstrated that the MMPs were mainly expressed by macrophages and Schwann cells. The biopsies with endoneurial inflammatory infiltrates and epithelioid granulomas had the highest levels of MMP-2 and MMP-9 mRNA detected. Together, these results suggest that M. leprae and TNF may directly induce Schwann cells to upregulate and secrete MMPs regardless of the extent of inflammation in leprous neuropathy.
Oliveira
Ariane Leite
AL
Leprosy Laboratory, Oswaldo Cruz Institute, Rio de Janeiro, Brazil.
Antunes
Sérgio Luiz Gomes
SL
Teles
Rosane Magda
RM
Costa da Silva
Ana Caroline
AC
Silva
Tatiana Pereira da
TP
Brandão Teles
Rose
R
Ferreira Medeiros
Mildred
M
Britto
Constança
C
Jardim
Márcia Rodrigues
MR
Pereira Sampaio
Elizabeth
E
Nunes Sarno
Euzenir
E
D000328:Adult; D000704:Analysis of Variance; D045744:Cell Line, Tumor; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D006801:Humans; D007918:Leprosy / Q000209:etiology* / Q000473:pathology*; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D008875:Middle Aged; D009166:Mycobacterium leprae / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009442:Neurilemmoma / Q000473:pathology; D010523:Peripheral Nervous System Diseases / Q000201:enzymology* / Q000382:microbiology; D012583:Schwann Cells / Q000201:enzymology*; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D015854:Up-Regulation / Q000502:physiology
D009419:Nerve Tissue Proteins; D019715:Tissue Inhibitor of Metalloproteinase-1; D014409:Tumor Necrosis Factor-alpha; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9