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

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

This article has been cited by other articles:

				W. MacNee Treatment of stable COPD: antioxidants Eur. Respir. Rev., September 1, 2005; 14(94): 12 - 22. [Abstract] [Full Text] [PDF]

				L. Xing and D. G. Remick Mechanisms of Dimethyl Sulfoxide Augmentation of IL-1{beta} Production J. Immunol., May 15, 2005; 174(10): 6195 - 6202. [Abstract] [Full Text] [PDF]

				W. MacNee Pulmonary and Systemic Oxidant/Antioxidant Imbalance in Chronic Obstructive Pulmonary Disease Proceedings of the ATS, April 1, 2005; 2(1): 50 - 60. [Abstract] [Full Text] [PDF]

				F. Antonicelli, D. Brown, M. Parmentier, E. M. Drost, N. Hirani, I. Rahman, K. Donaldson, and W. MacNee Regulation of LPS-mediated inflammation in vivo and in vitro by the thiol antioxidant Nacystelyn Am J Physiol Lung Cell Mol Physiol, June 1, 2004; 286(6): L1319 - L1327. [Abstract] [Full Text] [PDF]

				M. Song, J. A. Kellum, H. Kaldas, and M. P. Fink Evidence That Glutathione Depletion Is a Mechanism Responsible for the Anti-Inflammatory Effects of Ethyl Pyruvate in Cultured Lipopolysaccharide-Stimulated RAW 264.7 Cells J. Pharmacol. Exp. Ther., January 1, 2004; 308(1): 307 - 316. [Abstract] [Full Text] [PDF]

				Y. H. Cho, C. H. Lee, and S. G. Kim Potentiation of Lipopolysaccharide-Inducible Cyclooxygenase 2 Expression by C2-Ceramide via c-Jun N-Terminal Kinase-Mediated Activation of CCAAT/Enhancer Binding Protein beta in Macrophages Mol. Pharmacol., March 1, 2003; 63(3): 512 - 523. [Abstract] [Full Text] [PDF]