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Medical AI Inquiry: You was designed to assist in medical decision-making based on the provided user questions. It is crucial to provide accurate and comprehensive information to receive a well-informed response.  Labels: BACKGROUND, METHODS, RESULTS. Meshes: Animals, Cell Survival, Cells, Cultured, Drug Interactions, Enzyme-Linked Immunosorbent Assay, Inflammation, Interleukin-1, Interleukin-10, Interleukin-6, Lipopolysaccharides, Macrophages, Mice, Nitric Oxide, RNA, Messenger, Tumor Necrosis Factor-alpha, omega-N-Methylarginine.
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Does nitric oxide modulate pro- and anti-inflammatory cytokines in lipopolysaccharide-activated macrophages? Context: Sepsis is a serious and life-threatening syndrome that occurs in intensive care unit patients. Lipopolysaccharide (LPS) has been implicated as one of major causes of sepsis. Nitric oxide (NO) and cytokines are involved in sepsis-induced inflammatory responses. This study is aimed at evaluating the effects of NO on the modulation of pro- and anti-inflammatory cytokines in LPS-activated macrophages and its possible mechanism. N-Monomethyl arginine (NMMA), an inhibitor of NO synthase, was used in this study to suppress NO production. Mouse macrophage-like Raw 264.7 cells were exposed to LPS, NMMA, or a combination of NMMA and LPS. Cell viability was determined by the colorimetric 3-(4,5-dimethylthiazol-2-yl)-2,5-di-phenyltetrazolium bromide assay. The amounts of nitrite, an oxidative product of NO, in the culture medium were quantified according to the Griess reaction method. Enzyme-linked immunosorbent assay and reverse-transcriptase polymerase chain reaction were carried out to determine the expression of tumor necrosis factor (TNF)-alpha, interleukin (IL)-1 beta, and IL-10 in macrophages. Exposure of macrophages to LPS, NMMA, and a combination of NMMA and LPS for 24 hours did not affect cell viability. LPS significantly increased the amounts of nitrite in macrophages (p < 0.01). Treatment with NMMA decreased LPS-enhanced nitrite (p < 0.01) in a concentration-dependent manner. Analyses of enzyme-linked immunosorbent assays and reverse-transcriptase polymerase chain reaction revealed that LPS significantly induced TNF-alpha, IL-1 beta, and IL-10 proteins and mRNA (p < 0.01). A combined treatment with NMMA and LPS significantly blocked LPS-induced TNF-alpha and IL-1 beta (p < 0.01), but synergistically enhanced LPS-induced IL-10 (p < 0.05) protein and RNA.
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This study has shown that NO suppression can inhibit LPS-induced TNF-alpha and IL-1 beta but enhance IL-10, and the modulation occurs at a pretranslational level. Final Decision: yes