High, but not low, molecular weight hyaluronan prevents T-cell-mediated liver injury by reducing proinflammatory cytokines in mice (original) (raw)

The extracellular matrix component hyaluronan (HA) modulates the production of various cytokines and chemokines by activated inflammatory cells. In this study, we investigated whether exogenous administration of HA influences T-cell-mediated liver injury and cytokine production.

Methods

Liver injury was induced by administration of concanavalin A (Con A) or D-galactosamine/lipopolysaccharide (GalN/LPS), and 0.05%–0.35% (v/v) HA (MW 250, 470, 780, 900, and 1200 kDa) was administered intravenously 18 h before Con A or GalN/LPS injection. Plasma ALT level was determined enzymatically and plasma cytokine levels were determined by ELISA.

Results

The elevated plasma levels of ALT at 8 h after Con A and at 7 h after GalN/LPS injection were significantly decreased by pretreatment with high molecular weight HAs (780, 900, and 1200 kDa) but not low molecular weight HAs (250 and 470 kDa). High molecular weight HA (900 kDa) significantly reduced plasma tumor necrosis factor-alpha, interferon gamma, macrophage inflammatory protein 2, and interleukin 4 levels after Con A injection. However, this inhibitory effect on plasma cytokines was not observed with low molecular weight HA (250 kDa) pretreatment.

Conclusions

The present results suggest that high molecular weight but not low molecular weight HA prevents liver injury by reducing proinflammatory cytokines in a T-cell-mediated liver injury model.