title: Induction of multiple sclerosis and response to tyrosine kinase inhibitors.
abstract: The goal of this work is to determine the role of the autoimmune cells in multiple sclerosis (MS) induction and the immunomodulatory mechanism of therapy with tyrosine kinase inhibitors (TKIs) in MS attenuation. Samples (5 × 10(5) cells per well) of C6 and primary rat astrocytes were stimulated with 10 ng/mL of platelet-derived growth factor (PDGFbb) as a positive control forming a mouse model of MS. PDGFbb was added to the astrocytes in the absence or presence of 0.1 and 1 μM of imatinib. Proliferation of C6 and primary rat astrocytes samples were assessed for samples staging by the addition of 1 μCi of (3)H-thymidine per well. Samples of RAW 264.7 cells were stimulated for 48 h with 10 ng/mL of PDGFbb in the absence or presence of 0.1 and 1 μM of sorafenib. Tumour necrotic factor (TNF) levels in culture supernatants from RAW 264.7 cells were measured by ELISA. The histologic grade (HG) and the level of TNF of the mouse model of MS was 1/5 and 5 times respectively of those in the control one to clarify that MS induction is due to a major decrease in HG inversely proportional to the accompanied increase in TNF level perpetuating local inflammation and demyelination in MS lesion. The addition of 0.1 and 1 μM doses of imatinib increased HG of the mouse model of MS by 6 and 11 times respectively while 0.1 and 1 μM doses of sorafenib decreased TNF level to be 1/2 and 1/5 of that in the mouse model of MS respectively restoring normal rate of TNF level of normal lesion to show that HGand TNF level would be strongly inversely correlated (r = -0.99) in attenuating MS effectively by TKIs therapy but not in an inverse proportion as in MS induction.
authors.affiliation: Faculty of Engineering, Ain Shams University, Cairo, Egypt ; 217 Alhegaz Street, Alnozha, Cairo, 11351 Egypt.
authors.forename: Emad Y
authors.initials: EY
authors.lastname: Moawad
keywords: Histologic grade; Platelet-derived growth factor; Tumour necrotic factor