21st European Workshop for Rheumatology Research
- Meeting abstract
Thymosin beta4 sylphoxide: potential role in resolution of inflammation?
Arthritis Research & Therapy volume 3, Article number: P099 (2001)
Thymosin beta 4 sulphoxide (Tb4so) has previously been shown to be produced by glucocorticoid-treated monocytes (1). This highly conserved intracellular peptide possesses 'moonlighting' functions in the modulation of inflammatory responses, and may represent a natural down-regulator of inflammation in vivo. We have investigated the mechanisms of action of Tb4so primarily on neutrophils by studying its effects on in vitro and in vivo models.
Effect of Tb4so on assays of neutrophil function included chemotaxis and respiratory burst. Apoptosis was measured as Annexin-V/PI binding by FACS and macrophages were stained for phagocytic uptake of apoptotic neutrophils by the presence of neutrophil-specific myeloperoxidase. In vivo, the effect of administration of Tb4so on carrageenan-induced inflammation was eplored.
Tb4so significantly inhibited fMLP-induced chemotaxis (P < 0.005) and respiratory burst of human neutrophils in a dose dependent manner (100% vs 23%, P < 0.05). Further, it increased the rate of apoptosis in neutrophils (20.5 ± 1.9%, P < 0.05) and their subsequent phagocytic uptake by macrophages. In vivo, Tb4so was a potent inhibitor of neutrophil mediated carrageenan-induced inflammation in BALB/c mice (1.2 mm vs 0.6 mm P < 0.001 at 24 h).
Tb4so is an anti-inflammatory peptide that down-regulates neutrophil mediated inflammation. The mechanism of action appears to be, at least in part, via induction of neutrophil apoptosis and their clearance by phagocytic macrophages. These results suggest therapeutic potential for Tb4so.
Young , et al: Nature Med. 1999, 5: 1424-10.1038/71002.
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Young, J., Gracie, J., Stevenson, R. et al. Thymosin beta4 sylphoxide: potential role in resolution of inflammation?. Arthritis Res Ther 3, P099 (2001). https://doi.org/10.1186/ar268
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