TSP1 is a true adipokine that is highly expressed in obese, insulin-resistant subjects; is highly correlated with adipose inflammation; and is decreased by pioglitazone.
TSP1 enhances covalent modification of the inter-alpha-trypsin inhibitor by TSG-6 and transfer of its heavy chains to hyaluronan, suggesting a physiological function of TSP1 binding to TSG-6 in regulation of hyaluronan metabolism at sites of inflammation.
We conclude that DC-derived TSP serves as a previously unappreciated negative regulator contributing to arrest of cytokine production, further supporting its fundamental role in vivo in the active resolution of inflammation and maintenance of steady state.