Early heme oxygenase 1 induction delays tumour initiation and enhances DNA damage repair in liver macrophages of Mdr2^-/- mice.

ABSTRACT: Multi drug resistance protein 2 knockout mice (Mdr2^-/-) are a mouse model of chronic liver inflammation and inflammation-induced tumour development. Here we investigated the kinetics of early heme oxygenase 1 (HO-1) induction on inflammation, tumour development, and DNA damage in Mdr2^-/- mice. HO-1 was induced by intraperitoneal injection of cobalt protoporphyrin IX (CoPP) twice weekly for 9 consecutive weeks. Immediately after HO-1 induction, liver function improved and infiltration of CD4⁺ and CD8⁺ T cells was reduced. Furthermore, we observed increased p38 activation with concomitant reduction of Cyclin D1 expression in aged Mdr2^-/- mice. Long-term effects of HO-1 induction included increased CD8⁺ T cell infiltration as w

SUBMITTER: Barikbin R 

PROVIDER: S-EPMC6214975 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature