Regulation of lipopolysaccharide-mediated interleukin-1 beta release by N-acetylcysteine in THP-1 cells

Increased levels of inflammatory cytokines such as interleukin (IL)-1 and I L-8 occur in the bronchoalveolar lavage fluid in various lung diseases. Cyt okine gene expression is controlled by transcription factors such as nuclea r factor-kappaB (NF-kappaB) which can be activated by a number of stimuli i ncluding the oxidants prevent. It was hypothesized that lipopolysaccharide (LPS)-induced IL-1 beta secretion may be modulated by the intracellular thi ol redox status of the cells. The effect of the antioxidant compound, N-acetyl-L-cysteine (NAC), on IL-1 beta release and regulation of NF-kappaB in a human myelo-monocytic cell li ne (THP-1) differentiated into macrophages was studied. LPS (10 mug.mL(-1)) increased IL-1 beta release at 24 h compared to control levels (p<0.001). NAC (5 mM) also enhanced LPS-induced IL-1<beta> release from THP-1 cells (p<0.001). In addition, treatment of cells with cyclohexim ide, an inhibitor of protein synthesis, inhibited the NAC-mediated IL-1<bet a> release. Under the same conditions, NF-kappaB binding was activated by L PS and NAC increased this LPS-mediated effect. Western blot analysis reveal ed that NAC treatment leads to an increase in p50 and p65 protein synthesis . These data indicate that N-acetyl-L-cysteine modulates interleukin-1 beta r elease by increasing levels of the homo- and heterodimeric forms of nuclear factor-kappaB.