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Polyclonal immunoglobulins (IVIg) induce expression of MMP-9 in microglia
R Pul1, T Kopadze, T Skripuletz
1Department of Neurology, Hannover Medical School, Hannover, Germany.
Abstract:
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.
Insights
Intact intravenous immunoglobulin (IVIg) increases matrix metalloproteinase-9 (MMP-9) secretion in resting microglia. This suggests IVIg may modulate immune responses in multiple sclerosis (MS) by affecting MMP-9 production.
Area of Science:
- Neuroimmunology
- Molecular Biology
Background:
- Matrix metalloproteinases (MMPs), particularly MMP-9, are implicated in multiple sclerosis (MS) pathogenesis, contributing to blood-brain barrier disruption and demyelination.
- Activated microglia are known secretors of MMPs, making them a potential target for therapeutic modulation in MS.
Purpose of the Study:
- To investigate the effect of intact polyclonal immunoglobulins for intravenous use (IVIg) and their fragments on MMP-9 secretion in microglia.
- To determine if IVIg influences MMP production in both resting and activated microglia.
Main Methods:
- Primary microglia cultures were treated with intact IVIg or F(ab')(2) fragments.
- Lipopolysaccharide (LPS) was used to stimulate microglia activation.
- MMP-9 secretion levels were measured.
- RT-PCR was employed to detect the expression of various MMPs (MMP-2, -3, -7, -10, -11, -12).
Main Results:
- Intact IVIg significantly increased MMP-9 secretion in unstimulated (resting) microglia.
- F(ab')(2) fragments and LPS stimulation did not affect MMP production.
- No significant expression of MMP-2, -3, -7, -10, -11, or -12 was detected via RT-PCR under any condition.
Conclusions:
- Intact IVIg differentially modulates MMP-9 production in microglia, specifically increasing it in resting cells.
- This suggests an activation-dependent immune response where IVIg's effect on MMP-9 is context-specific.
- Findings highlight a potential mechanism for IVIg in MS treatment by influencing MMP-9 levels.
