02829nas a2200481   4500000000100000008004100001260001300042653001000055653002500065653002100090653003800111653001100149653001100160653001200171653000900183653003100192653003100223653001600254653002500270653002600295653001700321653003900338653001800377653004400395653003200439653001800471100001600489700001400505700001300519700002200532700001300554700002100567700002400588700001300612700001400625700002200639700001200661245014700673300001000820490000700830520149600837022001402333       2010                            d  c2010 Jan10aAdult10aAnalysis of Variance10aCell Line, Tumor10aEnzyme-Linked Immunosorbent Assay10aFemale10aHumans10aleprosy10aMale10aMatrix Metalloproteinase 210aMatrix Metalloproteinase 910aMiddle Aged10aMycobacterium leprae10aNerve Tissue Proteins10aNeurilemmoma10aPeripheral Nervous System Diseases10aSchwann Cells10aTissue Inhibitor of Metalloproteinase-110aTumor Necrosis Factor-alpha10aUp-Regulation1 aOliveira AL1 aAntunes S1 aTeles RM1 aCosta da Silva AC1 aSilva TP1 aBrandão Teles R1 aFerreira Medeiros M1 aBritto C1 aJardim MR1 aPereira Sampaio E1 aSarno E00aSchwann cells producing matrix metalloproteinases under Mycobacterium leprae stimulation may play a role in the outcome of leprous neuropathy.  a27-390 v693 a<p>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.</p>  a1554-6578