engleski

Osteopontin as early marker of developing experimenal autoimmune encephalomyelitis in rats

Osteopontin (Opn) is an O-glycosylated phosphoprotein that is synthesized in a variety of tissues and cells and has pleiotropic functions including roles in inflammation and in immunity. Secreted form of Opn acts as a Th1 cytokine and as a chemoattractant for many types of cells through integrin receptors and CD44. Recently, it has been shown that intracellular form of Opn is a critical regulator for TLR-9, TLR-7-dependent interferon-α expression by plasmacytoid DCs and Th17 development. Furthermore, OPN expression is frequently up-regulated in response to various stressors, when it promotes cell survival. Additionally, in inflammatory situations OPN stimulates both pro- and anti-inflammatory processes, what can be either beneficial or harmful depending on other inputs on the cells. In this study we estimated the expression of OPN in the brain, spinal cord, liver and the thymus early in the course of chronic relapsing experimental autoimmune encephalomyelitis (CR-EAE) pathogenesis, i.e. before the onset of any clinical symptoms. Disease was induced in the genetically susceptible Dark Agouti (DA) rats by subcutaneous injection of bovine brain homogenate in complete Freund’s adjuvant (CFA). Control animals were treated with CFA alone. The data obtained by immunofluorescence have shown that in the presymptomatic phase of CR-EAE (on the seventh post-immunization day) OPN was markedly upregulated in the brain parenchyma and blood vessels, as well as in the spinal cord neurons. Furthermore, we found that shortly after immunization OPN was also induced in the liver and the thymus. The data point to the role of OPN early during the CR-EAE development, in the CNS as a target tissue, but also in the liver, as the site of acute phase response and in the thymus, as a place of autoreactive clones generation.

osteopontin; EAE; DA rats

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