Abstract
The elderly are more susceptible to sepsis, which is often fatal, and caused by infection and characterized by systemic inflammation and oxidative stress. Blood monocytes are effector immune cells that play critical roles in the pathogenesis of sepsis through producing large amount of pro-inflammatory cytokines and oxidants. In this study we examined glutathione (GSH) content, expression of Nrf2-regulated antioxidant genes (GCLC, GCLM, HO-1, and NQO1) and NF- B-regulated inflammatory genes (TNF , IL-1 , IL-6, and IL-8), and their induction in response to lipopolysaccharide (LPS), in human blood monocytes from young (ages 20–40 years) and old (ages >60 years) donors. Our results showed that at basal condition, the intracellular GSH content and the mRNA level of GCLC were decreased in the old monocytes, while the expression of other antioxidant genes and pro-inflammatory genes was not changed with aging. Upon LPS exposure, the expression of all four antioxidant genes was decreased, while that of the pro-inflammatory genes increased, in the old monocytes. In conclusion, our data demonstrated that Nrf2-regulated antioxidant genes was suppressed in response to LPS in human blood monocytes, and that a greater inflammatory response was elicited by LPS in monocytes from the elderly.
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