Article
Schwann Cells Producing Matrix Metalloproteinases Under Mycobacterium leprae Stimulation May Play a Role in the Outcome of Leprous Neuropathy
Registro en:
OLIVEIRA, Ariane Leite; et al. Schwann Cells Producing Matrix Metalloproteinases Under Mycobacterium leprae Stimulation May Play a Role in the Outcome of Leprous Neuropathy. J. Neuropathol Exp Neurol., v.69, n.1, p.27-39, Jan. 2010.
0022-3069
1554-6578
Autor
Oliveira, Ariane Leite
Antunes, Sérgio Luiz Gomes
Teles, Rosane Magda
Silva, Ana Carolina Costa da
Silva, Tatiana Pereira da
Teles, Rose Brandão
Medeiros, Mildred Ferreira
Britto, Constança
Jardim, Márcia Rodrigues
Sampaio, Elizabeth Pereira
Sarno, Euzenir Nunes
Resumen
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. 2030-01-01