02540nas a2200433   4500000000100000008004100001260001300042653001800055653001900073653001000092653002300102653001100125653003500136653001100171653002500182653001200207653000900219653003100228653003100259653001600290653002200306653005200328653000800380653003200388100001200420700001400432700001300446700001500459700001200474700001200486700001400498700001500512700001200527245011100539300001200650490000700662520142300669022001402092       2007                            d  c2007 Sep10aADAM Proteins10aADAM17 Protein10aAdult10aDNA, Complementary10aFemale10aFluorescent Antibody Technique10aHumans10aImmunohistochemistry10aleprosy10aMale10aMatrix Metalloproteinase 210aMatrix Metalloproteinase 910aMiddle Aged10aPeripheral nerves10aReverse Transcriptase Polymerase Chain Reaction10aRNA10aTumor Necrosis Factor-alpha1 aTeles R1 aAntunes S1 aJardim M1 aOliveira A1 aNery JA1 aSales A1 aSampaio E1 aShubayev V1 aSarno E00aExpression of metalloproteinases (MMP-2, MMP-9, and TACE) and TNF-alpha in the nerves of leprosy patients.  a195-2040 v123 a<p>Matrix metalloproteinases (MMPs) and tumor necrosis factor alpha (TNF-alpha) play important and related roles in the pathogenesis of nerve injury. MMP-dependent and TNF-alpha-dependent processes of neurodegeneration, such as blood-nerve breakdown and immune cell recruitment, are characteristic of leprosy nerve damage. Our work has contributed to the understanding of the role of cytokines in the process, but the role of MMPs in the pathogenesis of neuritic leprosy has not been investigated. This study analyzed the changes in mRNA expression and immunodistribution of MMP-2, MMP-9, TNF-alpha-converting enzyme (TACE), TNF-alpha in nerves of 27 pure neuritic leprosy (PNL) patients, both acid-fast bacilli positive (AFB(+)) and acid-fast bacilli negative (AFB(-)), and 8 non-leprosy patients with control peripheral neuropathic conditions. MMP-2, MMP-9, and TNF-alpha mRNA expression was significantly induced in the AFB(-) relative to the AFB(+) neuritic leprosy group and nonlepritic controls; TACE levels were also elevated in the AFB(-) group, but this change was not statistically significant. Immunoreactive profiles for TNF-alpha and MMPs demonstrated strong reactivity of myelinated axons, infiltrating macrophages, Schwann cells, endothelial cells, and perineurial cells in neuritic leprosy biopsies. This study provides the evidence of the involvement of MMPs in the pathogenesis of PNL neuropathy.</p>  a1085-9489