Contribution of Receptors, Transcription Factors, and Genes in the Induction of Neuroinflammation

Abstract

Microglial cells are the resident immune surveillance cells of the brain. They ac-count for 10 % of the total glial cell population in the brain. Microglial cells serve as the first line of defense against pathogens entering the brain parenchyma and thus, play an important role during injury and infection in the brain (Raivich 2005). Under normal conditions, resting microglial cells interact with their surroundings and provide neurotrophic factors. Resting microglia express low levels of several key surface receptors, including the tyrosine phosphatase (CD) 45 (also known as leukocyte common antigen), CD-14, and CD11b/CD18 (Mac-1) (Kreutzberg 1996). In addition cell surface receptor-ligand pairs such as CD200R/CD200 are present to maintain neuron-glia communication in the brain (Cardona et al. 2006). However, under pathological conditions, microglia are transformed into a reactive or activated state not only by localized changes in the environment, but also by the influence of infiltrating blood-borne cells and disruption of local blood brain barrier (BBB), which plays an important role in maintaining the homeostatic environment of the brain, and damage to various structural and functional components of the BBB may contribute significantly to disease etiology or progression (Nimmerjahn et al. 2005). Activated microglia are characterized not only by increased expression of above mentioned key surface receptors, but also by up-regulation of proteins such as CD1, lymphocyte function-associated antigen 1 (LFA-1), intercellular adhesion molecule 1 (ICAM-1 or CD54), and vascular cell adhesion molecule (VCAM-1 or CD106). In addition, activated microglial cells secrete a variety of inflammatory mediators in-cluding cytokines (TNF-α, and interleukins IL-1β and IL-6) and chemokines (mac-rophage inflammatory protein MIP-1α, monocyte chemoattractant protein MCP-1 and interferon (IFN) inducible protein IP-10 that promote and maintain the inflam-matory state (Block and Hong 2005; Tansey and Wyss-Coray 2008). On one hand, it has been reported that microglia can produce growth factors, cytokines, and che-mokines that can promote the proliferation and recruitment of neural precursor cells to sites of injury (Aarum et al. 2003) supporting the view that microglial cells play an active role in host defense and tissue repair. For example production of IL-4 or low level of IFNγ is associated with increased neuroprotection (Baron et al. 2008).