Upregulation of heme oxygenase-1 in Kupffer cells blocks mast cell degranulation and inhibits dendritic cell migration in vitro

Abstract

Kupffer cells (KCs) influence liver allografts by interacting with other non-parenchymal cells. However, the exact mechanism remains unclear. Upregulation of heme oxygenase-1 (HO-1) in KCs upon interaction with mast cells (MCs), and the effects on dendritic cell (DC) function, were investigated in the present study. KCs, MCs and DCs were prepared from 8-10-week-old C57BL/6 mice. KCs were pretreated with PBS, dimethyl sulfoxide, hemin (50 μM; HO-1 inducer), and zinc protoporphyrin (50 μM; HO-1 inhibitor) for 8 h. Reverse transcription-polymerase chain reaction and western blotting was performed to determine HO-1 mRNA and protein levels in KCs, respectively. C-C motif chemokine receptor 7 (CCR7) surface molecules were measured using flow cytometry, and prostaglandin E2(PGE2), C-C motif chemokine ligand (CCL) 19 and CCL21 were measured by ELISA. The Transwell model was used to investigate the migration of DCs. Pretreatment of KCs with hemin induced HO-1 transcription and protein expression, and interacted with and stabilized MC membranes. When co-cultured with MCs, the expression of CCR7 on DCs was reduced, and PGE2, CCL19 and CCL21 were similarly decreased. DC migration was also impaired. Upregulation of HO-1 in KCs blocked MC degranulation and reduced DC migration.