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.