Thymosin Beta-4 Sulfoxide

Thymosin Beta-4 Sulfoxide (Tβ4-SO) is the oxidized form of thymosin beta-4, generated by the addition of an oxygen atom to the methionine-6 residue. Unlike the native peptide which sequesters G-actin intracellularly, Tβ4-SO is a potent extracellular anti-inflammatory signaling molecule generated by monocytes in the presence of glucocorticoids. It represents a biologically distinct entity with properties complementary to but different from parent TB-4.

Oxidation of Met-6 attenuates Tβ4's G-actin-sequestering activity while greatly enhancing its extracellular signaling properties. Tβ4-SO inhibits neutrophil chemotaxis and is thought to be the secreted, extracellular signaling form of the parent peptide. In vivo, Tβ4-SO — but not the native form — potently inhibits carrageenan-induced paw edema in mice. In cardiac models, Tβ4-SO attenuates inflammatory cell infiltration and promotes wound healing post-infarction. It may represent part of the mechanism by which glucocorticoids exert anti-inflammatory effects via monocyte-secreted peptides.

Key research by Bhatt et al. (1999, Nature Medicine) established Tβ4-SO as an anti-inflammatory monocyte product in the presence of glucocorticoids. A 2013 Nature Communications study demonstrated that Tβ4-SO reduces inflammatory infiltrate and promotes healing in murine cardiac injury models. At sites of inflammation, the respiratory burst oxidizes extracellular Tβ4 to the sulfoxide in vivo, suggesting Tβ4-SO is the physiologically active extracellular form.

Peptides commonly paired with Thymosin Beta-4 Sulfoxide for synergistic effects.