Abstract Details

Title Glatiramer Acetate Induced Intracellular Transgelin-2 Elevation Reduces MMP-9 Expression in Human Peripheral Blood Mononuclear Cells

Topic MS and Related Diseases

Presentation(s) P05 - (-)

Poster/Presentation
Number 147

Objective

Background BACKGROUND: It is well established that GA among other effects induces a shift in the cytokine profile of T-cells. As the molecular mechanisms involved are largely unknown, we investigated the regulated proteome of GA specific and MBP specific T-cell lines (TCL).

Design/Methods DESIGN/METHODS: We applied 2D gel electrophoresis combined with mass spectrometry to identify proteins regulated in GA and MBP specific TCL generated from healthy individuals and identified 10 proteins differently regulated. Pathway analysis of these proteins led us besides a group of antioxidative proteins to TAGLN2, upregulated only in GA specific TCL. To validate our proteomic results, we established western blot and ELISA analysis for TAGLN2 in human PBMC of healthy subjects.

Results RESULTS: Intracellular protein levels of TAGLN2 are upregulated in GA specific TCL compared to encephalitogenic MBP specific TCL as shown in our proteomic approach. In cultured ex vivo PBMC GA and TAGLN2 were able to inhibit MMP-9 expression compared to un-stimulated or TNF-? stimulated conditions. Western blot analysis of TAGLN2 expression revealed a significant elevation of TAGLN2 levels in GA stimulated PBMCs. In TNF-? pre-stimulated cells incubation with TAGLN2 led to a significantly stronger inhibition of MMP-9 expression compared to un-stimulated culture conditions.

Conclusions CONCLUSIONS: GA is able to inhibit MMP-9 expression in human PBMCs. This effect seems to be mediated by the biological still poorly described protein TAGLN2 which especially under pro-inflammatory conditions reduced MMP-9 expression. These results indicate a so far unknown mechanism of GA. Our findings make TAGLN2 a highly interesting candidate for further investigation and novel option of MS-therapy.

Authors/Disclosures
Matthias Knop PRESENTER	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file

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