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A Cell-Penetrating Peptide for Inhibiting MAPKAP Kinase 2-Mediated Inflammatory Cytokine Release Following Glial Cell Activation

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DOI: 10.4236/wjns.2015.52014    2,333 Downloads   2,683 Views  

ABSTRACT

Central nervous system (CNS) injury initializes a reactive tissue response, which is characterized by a cascade of signals that result in inflammatory cytokine release and neuroinflammation. These signals are induced in part by activated microglia that migrates to the injury site in an attempt to remove dead tissue and promote healing. The ability to control the reactive tissue response is of significant importance to a variety of applications, such as neuroprostheses, whose functional lifespan is limited by glial cell activation. A possible strategy to mitigate glial cell activation is to reduce the release of inflammatory cytokines following a brain injury. One pathway that facilitates inflammatory cytokine release is the mitogen-activated protein kinase-activated protein kinase 2 (MK2) pathway, which increases cytokine mRNA synthesis, stability and translation following activation. Therefore, inhibiting MK2-mediated cytokine release can reduce microglial activationfollowing CNS injury. Through in vitro studies, we demonstrate the ability of a cell-penetrating peptide inhibitor of MK2 (MK2i) to reduce MK2-mediated cytokine release in mixed cortical cultures. Immunocytochemistry, enzyme-linked immunosorbent assay (ELISA), and cytotoxicity assays in 7- -10-day-old E17 Sprague-Dawley rat mixed cortical cultures showed that MK2i treatment significantly lowered inflammatory cytokine production and increased cortical cell viability following glial cell activation with tumor necrosis factor-α(TNF-α) and lipopolysaccharide (LPS). Results suggest that MK2i may reduce damage caused by activated glia in the inflamed CNS.

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Wodicka, J. , Onunkwo, N. , Woolley, A. , Panitch, A. and Otto, K. (2015) A Cell-Penetrating Peptide for Inhibiting MAPKAP Kinase 2-Mediated Inflammatory Cytokine Release Following Glial Cell Activation. World Journal of Neuroscience, 5, 115-130. doi: 10.4236/wjns.2015.52014.

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