Effect of natalizumab treatment on metalloproteinases and their inhibitors in a mouse model of multiple sclerosis.

Effect of natalizumab treatment on metalloproteinases and their inhibitors in a mouse model of multiple sclerosis. J Physiol Pharmacol. 2020 Apr;71(2): Authors: Pyka-Fosciak G, Lis GJ, Litwin JA Abstract Matrix metalloproteinases (MMPs) regulated by their tissue inhibitors (TIMPs) play a significant role in the pathogenesis of multiple sclerosis (MS) and its mouse model, experimental autoimmune encephalomyelitis (EAE), as they degrade extracellular matrix including vascular basal laminae and by damaging blood-brain barrier (BBB) facilitate transmigration of immune cells into the central nervous system. MMPs are also involved in destruction of myelin sheaths, leading to axonal and neuronal loss. The aim of the present study was to assess whether natalizumab, a transmigration-inhibiting monoclonal antibody against α4β1 integrin, influences expression of MMPs and TIMPs in the central nervous system of mice with EAE. MMP-2 and MMP-9, their respective inhibitors TIMP-2 and TIMP-1 and laminin were assessed by quantitative immunohistochemistry in the spinal cord cryosections of C57BL/6 mice with EAE in the successive phases of the disease (onset, peak and chronic). The percentage of immunopositive areas were calculated in sections encompassing the whole spinal cord cross-sectional area occupied by the gray and white matter. Results obtained in animals administered with 5 mg/kg natalizumab were compared with those collected from control mi...
Source: Journal of Physiology and Pharmacology - Category: Drugs & Pharmacology Tags: J Physiol Pharmacol Source Type: research