Abstract
Free 8-hydroxydeoxyguanosine (oh 8dG), a nucleoside of 8-hydroxyguanine (oh 8Gua), present in cytosol is not incorporated into DNA. However, nothing is known about its biological function when it presents in cytosol as a free form. We demonstrate here for the first time that oh 8dG inhibits lipopolysaccharide (LPS)-induced nitric oxide (NO) production and cyclooxygenase-2 (COX-2) activity, and both gene transcriptions in microglia. Furthermore, oh 8dG reduced mRNA levels of pro-inflammatory cytokine, such as IL-1β, IL-6, and TNF-α, in activated BV2 cells. We also found that oh 8dG suppressed reactive oxygen species (ROS) production through reduction of NADPH oxidase activity and blocked Rac1/STATs signal cascade. Finally, oh 8dG suppressed recruitment of STATs and p300 to the iNOS and COX-2 promoters, and inhibited H3 histone acetylation. Taken together, these results provide new aspects of oh 8dG as an anti-inflammatory agent.
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