Abstract
Chronic liver diseases, including cancer, are characterized by inflammation and elevated serum ferritin (SF). However, the causal-relationship remains unclear. This study used primary rat hepatic stellate cells (HSC) as a model to investigate effects of physiological SF concentrations (10, 100 and 1000 pM) because HSCs play a central role in the development and progression of liver fibrosis. Physiological concentrations of SF, either horse SF or human serum, induced pro-inflammatory cytokine IL1β, IL6 and TNFα secretion in rat activated HSCs (all p<0.05). By contrast, treatment did not alter activation marker aSMA expression. The presence of SF markedly enhanced expression of Grp78 mRNA (p<0.01). Furthermore, transient knock down of Grp78 by endotoxin EGF-SubA abolished SF-induced IL1β and TNFα secretion in activated HSCs (all p<0.05). In conclusion, our results showed that at physiological concentrations SF functions as a pro-inflammatory mediator in primary rat HSCs. We also provide a molecular basis for the action of SF and identified Grp78-associated ER stress pathways as a novel potential therapeutic target for resolution of fibrosis and possible prevention of liver cancer.
Original language | English |
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Pages (from-to) | 605-610 |
Number of pages | 6 |
Journal | Asian Pacific Journal of Cancer Prevention |
Volume | 15 |
Issue number | 2 |
DOIs | |
Publication status | Published - 2014 |
Externally published | Yes |
Keywords
- Endoplasmic reticulum stress
- Grp78
- Hepatic stellate cells
- Liver fibrosis
- Serum ferritin
ASJC Scopus subject areas
- Epidemiology
- Oncology
- Public Health, Environmental and Occupational Health
- Cancer Research