Regulation of Lymphotactin and Fractalkine Expression

Both lymphotactin and fractalkine are expressed in an activation-dependent manner. The expression of lymphotactin is upregulated by phorbol ester and concanavalin 1 in T-cells isolated from peripheral blood (Middel et al., 2001). It can be inhibited by anti-inflammatory steroid dexamethasone or immunosuppressive drugs such as cyclosporine A and FK506 (Middel et al., 2001). These agents also regulate the expression of lymphotactin receptor XCRl on T-cells in a manner similar to the regulation of lymphotactin expression. The nuclear factor of activated T-cells (NF-AT) family s transcription factors are likely to be involved in the activation-induced expression and cyclosporine A-dependent inhibition of lymphotactin (Yoshida et al., 1999). 

Fractalkine was first documented as a factor induced by TNF-a, interleukin-1 (IL-1), and bacterial lipopolysaccharide (LPS) (Bazan et al, 1997). TNF-a, IL-1, and LPS stimulate a similar spectrum of signal-transduction systems and activate both nuclear factor-KB (NF-kB) and mitogen-activated protein kinases (MAPKs). In rat aortic endothelial cells, the induction of fractalkine by these agonists is mediated through the NF-kB system (Garcia et al., 2000). 

Fractalkine is constitutively expressed in dendritic cells and upregulated upon dendritic cell maturation (Kanazawa et al, 1999). This suggests that fractalkine plays an important role in the intercellular communications during immune reactions. 

In the nervous system, fractalkine is constitutively expressed in the olfactory bulb, cerebral cortex, and hippocampus, among other places (Nishiyori et al., 1998), but its expression is not affected by experimentally induced inflammation of central nervous tissue (Schwaeble et al, 1998). TNF-a and IFN-y synergistically enhance the expression of fractalkine in cultured human astrocytes (Yoshida et al, 2001). IFN-y also enhances fractalkine expression in human bronchial epithelial cells, and the chemokine mediates adherence of macrophages (Fujimoto et al, 2001). Fractalkine is induced by TNF-a, IFN-y, and IL-4 in fibroblasts (Fahy et al, 2003 Yoshikawa et al, 2004). 

It has been known for some time that the soluble form of the IL-6 receptor possesses an agonistic activity towards vascular endothelial cells (Modur et al, 1997). IL-6 is a multifunctional cytokine and mediates a variety of inflammatory and cell-growth responses. The cell-surface receptor for IL-6 consists of a cytokine-binding a subunit (IL-6Ra) and a transmembranesignaling gpl30 subunit. Vascular endothelial cells lack IL-6Ra, but gpl30 

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