Polyclonal immunoglobulins (IVIg) induce expression of MMP-9 in microglia.
In multiple sclerosis (MS) matrix metalloproteinases (MMP) are believed to be involved in the disruption of the blood brain barrier and demyelination. MMP-9 is increased in the cerebrospinal fluid of MS patients and expressed in MS lesions, indicating an involvement in MS pathogenesis. It is known that activated microglia secrete MMP. Modulation of MMP may thus be of interest for treatment in particular since MMP knock-out mice are less susceptible to experimental allergic encephalomyelitis. In this study we show that intact polyclonal immunoglobulins for intravenous use (IVIg) lead to increased secretion of MMP-9 in unstimulated microglia whereas F(ab')(2) fragments or stimulation with lipopolysaccharide (LPS) had no effect on MMP production at all. We could not detect MMP-2, MMP-3, MMP-7, MMP-10, MMP-11, and MMP-12 by RT-PCR with and without stimulation with LPS. IVIg differentially modulate MMP-9 production in resting and activated microglia suggesting an activation-dependent immune response.
Pul
R
R
Department of Neurology, Hannover Medical School, Hannover, Germany.
Kopadze
T
T
Skripuletz
T
T
Voss
E V
EV
Kieseier
B C
BC
Stangel
M
M
D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000166:cytology; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000494:pharmacology*; D007155:Immunologic Factors / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism*; D017628:Microglia / Q000187:drug effects* / Q000201:enzymology; D009569:Nitric Oxide / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D016756:Immunoglobulins, Intravenous; D007155:Immunologic Factors; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D020780:Matrix Metalloproteinase 9