Expression of matrix metalloproteinase-9 and its inhibitors in mononuclearblood cells of patients with multiple sclerosis

Inflammatory mononuclear cells invading the nervous system in demyelinating diseases are supposed to be a major source of matrix metalloproteinases wh ich are involved in damaging the blood-brain barrier and facilitating cellu lar migration through the extracellular matrix. Several studies revealed a crucial role of 92 kDa gelatinase (matrix metalloproteinase-9, MMP-9) in th ese processes. In this study, we determined MMP-9, TIMP-1 and TIMP-2 (tissu e inhibitor of metalloproteinase) mRNA in peripheral blood mononuclear cell s of multiple sclerosis (MS) patients by competitive reverse transcription PCR and plasma protein levels by ELISA. In active MS patients, both with re lapsing-remitting and chronic progressive disease MMP-9 mRNA and plasma pro tein levels were significantly increased compared to healthy controls. No s ignificant changes in mRNA expression were found for TIMP-1 and TIMP-2. How ever, unbound TIMP-2 in plasma was significantly higher in MS patients comp ared to healthy controls. MMP-9 and TIMP-1 expression was significantly cor related in MS with a significantly higher MMP-9/TIMP-1 ratio in active MS t han in healthy controls. These results are in support of an important patho genic role of MMP-9 activity in MS. (C) 1999 Elsevier Science B.V. All righ ts reserved.