Cited by 519Immune Response and InflammationNF-κB Signaling PathwaysInflammasome and immune disorders

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Lipopolysaccharide-mediated Reactive Oxygen Species and Signal Transduction in the Regulation of Interleukin-1 Gene Expression

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Hsu, Hsien-Yeh, Wen, Meng-Hsuan·2002·Journal of Biological Chemistry

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Abstract

Lipopolysaccharide (LPS) stimulates macrophages to release inflammatory cytokines, interleukin-1 beta (IL-1), and tumor necrosis factor (TNF). LPS-induced TNF suppresses scavenger receptor functions in macrophages (van Lenten, B. J., and Fogelman, A. M. (1992) J. Immunol. 148, 112-116), which is regulated by TNF-mediated protein kinases (Hsu, H. Y., and Twu, Y. C. (2000) J. Biol. Chem. 275, 41035-41048). To examine the molecular mechanism for LPS induction of IL-1 in macrophages, we demonstrated that LPS quickly stimulated reactive oxygen species (ROS), and 3 h later induced prointerleukin-1 beta (pro-IL-1, precursor of IL-1) production and IL-1 secretion. LPS stimulated pro-IL-1 message/protein between 3 and 10 h; however, there was a 40% reduction of pro-IL-1 in preincubation of the antioxidant, N-acetylcysteine (NAC). Moreover, NAC moderated LPS-induced IL-1 secretion partially via interleukin 1-converting enzyme. The maximal activity of LPS-induced ERK, JNK, and p38 was 12- (30 min), 5- (30 min), and 16-fold (15 min), respectively. In contrast, NAC reduced ERK activity to 60% and decreased p38 activity to the basal level, but JNK activity was induced 2-fold. Furthermore, the pharmacological antagonists LY294002, SB203580, curcumin, calphostin C, and PD98059 revealed the diverse roles of LPS-mediated protein kinases in pro-IL-1. On the other hand, NAC and diphenyleneiodonium chloride partially inhibited LPS-induced Rac activity and protein-tyrosine kinase (PTK), indicating that LPS-mediated ROS and NADPH oxidase correspond to Rac activation and IL-1 expression. Our findings establish for the first time that LPS-mediated PTK/phosphatidylinositol 3-kinase/Rac/p38 pathways play a more important role than pathways of PTK/PKC/MEK/ERK and of PTK/phosphatidylinositol 3-kinase/Rac/JNK in the regulation of pro-IL-1/IL-1. The findings also further elucidate the critical role of LPS-mediated ROS in signal transduction pathways. Our results suggest that understanding LPS-transduced signals in IL-1 induction upon the antibacterial action of macrophages should provide a therapeutic strategy for aberrant inflammatory responses leading to severe cellular injury or concurrent multiorgan septic damage.

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Reactive Oxygen Species Modulation of the Mu-Opioid Receptor
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Self-citation
MACROPHAGE MIGRATION INHIBITORY FACTOR (MIF) MEDIATES LATE CARDIAC DYSFUNCTION FOLLOWING THERMAL INJURY
Willis, M. S., Carlson, D., DiMaio, M. J., White, M., White, J., Horton, J. W., & Giroir, B. P. (2004) · Shock · doi:10.1097/00024382-200403001-00320
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“또한, TNF-α 와 interleukin 1β와 같은 사이토카인과 케모카인의 분비를 통해 선천면역반응과 획득면역반응의 활성을 유도할 뿐만 아니라 과 도한 생물학적 반응을 유도하여 조직손상을 유발한다고 알려져 있다(Hsu and Wen, 2002).”
Activation of Caspase-1 Signaling Complexes by the P2X7 Receptor Requires Intracellular K + Efflux and Protein Synthesis Induced by Priming with Toll-Like Receptor Ligands
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Untersuchung von Zinksignalen während Aktivierung und Reifung in Monozyten
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“It is known that activated macrophages secrete reactive oxygen species (ROS) such as nitric oxide which has a cytotoxic effect against pathogens.(4) As ROS have a strong autofluorescence,(5) imaging this response can provide some indication on the activation state of macrophages, which is based on the concentration of…”
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Effect of Remote Ischemic Conditioning on Lipopolysaccharide-induced Pulmonary Inflammation
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Nanoparticle-mediated Cell Behavior Modulation for the Treatment of Myocardial Infarction
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Anti-Inflammatory Properties of Acerola (Malpighia emarginata) Leaf and Ripe Fruit Genotypes for Protection Against LPS-Induced Inflammation in Macrophage Cells and Their Selectivity to Cyclooxygenase-2 (COX-2) Activity
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Peroxiredoxin 2 Inhibits Lipopolysaccharide Induced Mucin Expression and Reactive Oxygen Species Production in Human Airway Epithelial Cells
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Authors: Hsu, H.-Y., & Wen, M.-H.
Affiliations: National Yang Ming University (TW)
Corresponding author: Hsu, Hsien-Yeh
ORCID: Wen, Meng-Hsuan
Venue: Journal of Biological Chemistry
Publisher: Elsevier BV
Published: 2002-06
Volume: 277
Issue: 25
Pages: 22131-22139
ISSN: 0021-9258 (ISSN-L)
DOI: 10.1074/jbc.m111883200
OpenAlex: W2016146035
Cited by: 519
References: 72
Citations by year: 2026: 13 · 2025: 17 · 2024: 20 · 2023: 21 · 2022: 21 · 2021: 27 · 2020: 22 · 2019: 23 · 2018: 25 · 2017: 33 · 2016: 27 · 2015: 21 · 2014: 18 · 2013: 19 · 2012: 14
FWCI: 7.22
Type: journal article
Language: en
Open access: hybrid
doi.org
Licence: cc-by
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
creativecommons.org/licenses/by/4.0/ (vor, 6719 d)
Locations: Journal of Biological Chemistry (publishedVersion, cc-by)
PubMed (publishedVersion)
Topics: Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › NF-κB Signaling Pathways
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Inflammasome and immune disorders
Keywords: lipopolysaccharide, IL-1β, reactive oxygen species, N-acetylcysteine, macrophages, Rac, p38 MAPK, JNK, ERK, phosphatidylinositol 3-kinase, tyrosine kinase, NADPH oxidase, signal transduction, inflammatory cytokines, TNF-α
MeSH terms: Animals, Carrier Proteins, Cell Line, Chromones, Curcumin, Enzyme Activation, Enzyme Inhibitors, Enzyme-Linked Immunosorbent Assay, Flavonoids, Gene Expression Regulation, Genes, Dominant, Imidazoles, Interleukin-1, Lipopolysaccharides, Macrophages, Models, Biological, Morpholines, Naphthalenes, Oxygen, Protein Binding, Pyridines, Time Factors, Transfection, Signal Transduction, Reactive Oxygen Species, rac1 GTP-Binding Protein, Mitogen-Activated Protein Kinases, Mitogen-Activated Protein Kinase Kinases, Intracellular Signaling Peptides and Proteins, JNK Mitogen-Activated Protein Kinases, p38 Mitogen-Activated Protein Kinases, MAP Kinase Kinase 4, Mice

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Lipopolysaccharide-mediated Reactive Oxygen Species and Signal Transduction in the Regulation of Interleukin-1 Gene Expression

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