Tetraspanin 8 Subfamily Members Regulate Substrate-Specificity of a Disintegrin and Metalloprotease 17.

Ectodomain shedding is an irreversible process to regulate inter- and intracellular signaling. Members of the a disintegrin and metalloprotease (ADAM) family are major mediators of ectodomain shedding. ADAM17 is involved in the processing of multiple substrates including tumor necrosis factor (TNF) α and EGF receptor ligands.

Inhibition of ADAM17 impairs endothelial cell necroptosis and blocks metastasis.

Metastasis is the major cause of death in cancer patients. Circulating tumor cells need to migrate through the endothelial layer of blood vessels to escape the hostile circulation and establish metastases at distant organ sites. Here, we identified the membrane-bound metalloprotease ADAM17 on endothelial cells as a key driver of metastasis.

Gut microbiota shape 'inflamm-ageing' cytokines and account for age-dependent decline in DNA damage repair.

Objective: Failing to properly repair damaged DNA drives the ageing process. Furthermore, age-related inflammation contributes to the manifestation of ageing. Recently, we demonstrated that the efficiency of repair of diethylnitrosamine (DEN)-induced double-strand breaks (DSBs) rapidly declines with age.

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

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.

The enhanced susceptibility of ADAM-17 hypomorphic mice to DSS-induced colitis is not ameliorated by loss of RIPK3, revealing an unexpected function of ADAM-17 in necroptosis.

The disintegrin metalloprotease ADAM17 has a critical role in intestinal inflammation and regeneration in mice, as illustrated by the dramatically increased susceptibility of ADAM17 hypomorphic (ADAM17) mice to dextran sulfate sodium (DSS)-induced colitis. Similarly, necroptosis has been implicated in inflammatory responses in the intestine. In this study, we have investigated the contribution of necroptosis to ADAM17-regulated intestinal inflammation by crossing ADAM17 mice with mice that lack the necroptotic core protein RIPK3.

IL-6 trans-signaling is essential for the development of hepatocellular carcinoma in mice.

Unlabelled: Hepatocellular carcinoma (HCC) is one of the most frequent tumors worldwide with rising incidence. The inflammatory cytokine, interleukin-6 (IL-6), is a critical mediator of HCC development. It can signal through two distinct pathways: the IL-6 classic and the IL-6 trans-signaling pathway.