title: Long-time treatment by low-dose N-acetyl-L-cysteine enhances proinflammatory cytokine expressions in LPS-stimulated macrophages.
abstract: N-acetyl-L-cysteine is known to act as a reactive oxygen species scavenger and used in clinical applications. Previous reports have shown that high-dose N-acetyl-L-cysteine treatment inhibits the expression of proinflammatory cytokines in activated macrophages. Here, we have found that long-time N-acetyl-L-cysteine treatment at low-concentration increases phosphorylation of extracellular signal-regulated kinase 1/2 and AKT, which are essential for the induction of proinflammatory cytokines including interleukin 1β and interleukin 6 in lipopolysaccharide-stimulated RAW264.7 cells. Furthermore, long-time N-acetyl-L-cysteine treatment decreases expressions of protein phosphatases, catalytic subunit of protein phosphatase-2A and dual specificity phosphatase 1. On the other hand, we have found that short-time N-acetyl-L-cysteine treatment at low dose increases p53 expression, which inhibits expressions of proinflammatory cytokines. These observations suggest that long-time low-dose N-acetyl-L-cysteine treatment increases expressions of proinflammatory cytokines through enhancement of kinase phosphorylation.
authors: Department of Oral Biochemistry, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan.
authors: Tomokazu
authors: T
authors: Ohnishi
authors: Department of Oral Biochemistry, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan.
authors: Kenjiro
authors: K
authors: Bandow
authors: Department of Oral Biochemistry, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan.
authors: Kyoko
authors: K
authors: Kakimoto
authors: Department of Oral Biochemistry, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan.
authors: Joji
authors: J
authors: Kusuyama
authors: Department of Oral Biochemistry, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan.
authors: Tetsuya
authors: T
authors: Matsuguchi
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology*; D000818:Animals; D002460:Cell Line; D016207:Cytokines / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D018836:Inflammation Mediators / Q000378:metabolism*; D007378:Interleukins / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D010749:Phosphoprotein Phosphatases / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D013997:Time Factors; D051193:Toll-Like Receptors / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; D007378:Interleukins; D008070:Lipopolysaccharides; D017382:Reactive Oxygen Species; D051193:Toll-Like Receptors; D016159:Tumor Suppressor Protein p53; D051057:Proto-Oncogene Proteins c-akt; D020928:Mitogen-Activated Protein Kinases; D010749:Phosphoprotein Phosphatases; D000111:Acetylcysteine