Modulation of microglial/macrophage activation by macrophage inhibitory factor (TKP) or tuftsin (TKPR) attenuates the disease course of experimental autoimmune encephalomyelitis

Abstract

Background: Myelin Oligodendrocyte Glycoprotein (MOG)-induced experimental autoimmune encephalomyelitis (EAE) is the most commonly used mouse model for multiple sclerosis (MS). During the of progression of EAE, microglia, the immunocompetent cells of the brain, become activated and accumulate around demyelinated lesions. Microglial activation is mediated by the extracellular protease tissue Plasminogen Activator (tPA), and mice lacking tPA display altered EAE progression. In this study, we have used pharmacological inhibitors and stimulators of microglial/ macrophage activation to examine the temporal requirement for microglial activation in EAE progression and to determine whether such approaches might potentially be of therapeutic value.

Activation of CB2 receptor is required for the therapeutic effect of ABHD6 inhibition in experimental autoimmune encephalomyelitis

“…Inhibition or depletion of microglia/macrophages has been shown to attenuate EAE progression (Berard et al, 2010a(Berard et al, , 2010bBhasin et al, 2007;Tran et al, 1998). It has been well-documented that microglia express cannabinoid receptors and produce 2-AG and anandamide (Carrier et al, 2004.…”

C16 peptide shown to prevent leukocyte infiltration and alleviate detrimental inflammation in acute allergic encephalomyelitis model

“…Several studies have demonstrated that macrophage/microglia activation and infiltration are essential for the development of clinical EAE (Raivich and Banati, 2004;Bhasin et al, 2007;Ponomarev et al, 2007). In particular, the activated microglia may produce a proinflammatory milieu, strip off myelin from axons, phagocytize myelin via receptor mediated pathways, disrupt the bloodebrain barrier (BBB) integrity and attract and activate T lymphatic cells and monocytes which could augment the destruction of myelin (Carson, 2002;Yin et al, 2010).…”

Differential roles of resident microglia and infiltrating monocytes in murine CNS autoimmunity

“…Administration of macrophage inhibitory factor (TKP) was also shown to result in attenuated EAE, supporting the notion that macrophage/microglia activation might contribute to CNS autoimmunity [52], although this approach did not differentiate between MoMF and microglia. In addition, constitutive activation of the NF-κB cascade in microglia/macrophages, such as in mice that lack the NF-κB inhibitor (LysM Cre :IκBα fl/fl ), resulted in aggravated EAE symptoms [53].…”