Expression of matrix metalloproteinase-9 and its inhibitors in mononuclear blood 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 which are involved in damaging the blood-brain barrier and facilitating cellular migration through the extracellular matrix. Several studies revealed a crucial role of 92 kDa gelatinase (matrix metalloproteinase-9, MMP-9) in these processes. In this study, we determined MMP-9, TIMP-1 and TIMP-2 (tissue inhibitor of metalloproteinase) mRNA in peripheral blood mononuclear cells of multiple sclerosis (MS) patients by competitive reverse transcription PCR and plasma protein levels by ELISA. In active MS patients, both with relapsing-remitting and chronic progressive disease MMP-9 mRNA and plasma protein levels were significantly increased compared to healthy controls. No significant changes in mRNA expression were found for TIMP-1 and TIMP-2. However, unbound TIMP-2 in plasma was significantly higher in MS patients compared to healthy controls. MMP-9 and TIMP-1 expression was significantly correlated in MS with a significantly higher MMP-9/TIMP-1 ratio in active MS than in healthy controls. These results are in support of an important pathogenic role of MMP-9 activity in MS.
Lichtinghagen
R
R
Institute of Clinical Chemistry I, Medizinische Hochschule, Hannover, Germany. lichtinghagen.ralf@mh-hannover.de
Seifert
T
T
Kracke
A
A
Marckmann
S
S
Wurster
U
U
Heidenreich
F
F
D000328:Adult; D001327:Autoimmune Diseases / Q000097:blood / Q000201:enzymology*; D017364:Collagenases / Q000096:biosynthesis* / Q000097:blood / Q000235:genetics; D003430:Cross-Sectional Studies; D018450:Disease Progression; D004790:Enzyme Induction; D004797:Enzyme-Linked Immunosorbent Assay; D005786:Gene Expression Regulation; D006801:Humans; D007962:Leukocytes / Q000201:enzymology*; D020780:Matrix Metalloproteinase 9; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000097:blood / Q000201:enzymology*; D012333:RNA, Messenger / Q000097:blood; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000096:biosynthesis* / Q000097:blood / Q000235:genetics; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000096:biosynthesis* / Q000097:blood / Q000235:genetics
D012333:RNA, Messenger; D019715:Tissue Inhibitor of Metalloproteinase-1; D019716:Tissue Inhibitor of Metalloproteinase-2; D017364:Collagenases; D020780:Matrix Metalloproteinase 9