Research Interests
The role of inflammatory cytokines in the development of autoimmunity
Currently a broad range of strategies to target inflammatory diseases are being explored. Most approaches require the identification of a single molecule/pathway (i.e. TNF-alpha, IL-15, IL-18). For example, in a series of studies, we have defined the mechanisms whereby IL-18 may promote the induction of inflammatory arthritis. These data identify IL-18 as a potential pro-inflammatory cytokine and should therefore be regarded as a potential therapeutic target, in RA and in other chronic autoimmune diseases in which similar pathophysiologic pathways are implicated. We’re currently studying the actions of these cytokines in a murine model of collagen-induced arthritis and its role in the pathogenesis of autoimmune diseases such as RA.
Role of anti-inflammatory compounds in experimental inflammatory models
A number of intracellular signalling cascades have been shown to be important in the activation of various immune cells/functions. Immune cell activates have shown to be modulated by the dynamic balance between sphingosine and sphingosine-1-phosphate (S1P). Blockade of sphingosine kinase (SphK) has broad anti-inflammatory activities and in particular is capable of reducing pro-inflammatory neutrophils and macrophages activities, angiogenesis and chemotaxis. We’re currently studying the role of SphK and inflammatory cytokines such as IL-33 in immuno-regulation.
Reduced lung inflammation and mucus production in mice treated with DMS, a SphK inhibitor. A, Naïve mouse with PBS challenge, B, OVA-challenged mouse with peribronchial and perivascular inflammatory infiltrates, together with eosinophilila and mucosal hyperplasia. C, OVA-challenged mouse treated with 200 m g/kg of DMS, and D, 400 m g/kg of DMS; a reduction in inflammation is seen compared with B. E, Histological appearances were scored for the presence of peribronical and perivasuclar inflammation, mucus production and goblet cell hyperplasia. (J. Immunol. 2008, 180:4323).
