LPS Induces Hypoxia-Inducible Factor 1 Activation in Macrophage-Differentiated Cells in a Reactive Oxygen Species–Dependent Manner

Autor: Kazuhiko Fukuda, Kiichi Hirota, Gregg L. Semenza, Satoshi Takabuchi, Koh Shingu, Kenichiro Nishi, Takehiko Adachi, Seiko Oda, Tomoyuki Oda
Rok vydání: 2008
Předmět:
Lipopolysaccharides
Lipopolysaccharide
Physiology
Cellular differentiation
Clinical Biochemistry
Lipopolysaccharide Receptors
Inflammation
Biology
Biochemistry
Cell Line
chemistry.chemical_compound
Genes
Reporter
medicine
Humans
Enzyme Inhibitors
RNA
Small Interfering
Molecular Biology
Transcription factor
General Environmental Science
chemistry.chemical_classification
Reactive oxygen species
Innate immune system
NADPH oxidase
Macrophages
NF-kappa B
Cell Differentiation
Cell Biology
Hypoxia-Inducible Factor 1
alpha Subunit
Toll-Like Receptor 2
Acetylcysteine
Cell biology
Toll-Like Receptor 4
NG-Nitroarginine Methyl Ester
Gene Expression Regulation
chemistry
Cell culture
Myeloid Differentiation Factor 88
biology.protein
General Earth and Planetary Sciences
Nitric Oxide Synthase
medicine.symptom
Reactive Oxygen Species
Zdroj: Antioxidants & Redox Signaling. 10:983-996
ISSN: 1557-7716
1523-0864
DOI: 10.1089/ars.2007.1825
Popis: A prominent feature of various inflamed and diseased tissue is the presence of low oxygen tension (hypoxia). Effector cells of the innate immune system must maintain their viability and physiologic functions in a hypoxic microenvironment. Monocytes circulating in the bloodstream differentiate into macrophages. During this process, cells acquire the ability to exert effects at hypoxic sites of inflammation. The transcription factor hypoxia-inducible factor 1 (HIF-1) mediates adaptive responses to reduced oxygen availability. In this study, we demonstrated that lipopolysaccharide (LPS) induces HIF-1 activation by enhancing both HIF-1alpha protein expression through a translation-dependent pathway and HIF-1alpha transcriptional activity in THP-1 human myeloid cells that have undergone macrophage differentiation but not in undifferentiated monocytic THP-1 cells. LPS-induced HIF-1 activation was blocked by treatment with antioxidant (N-acetylcysteine or thioredoxin-1), NADPH oxidase inhibitor (diphenyleneiodonium), indicating that reactive oxygen species generated in response to LPS are essential in this process. LPS-mediated activation of HIF-1 was independent of NF-kappaB activity. LPS-induced ROS generation and HIF-1 activation required the expression of Toll-like receptor 4 or myeloid differentiation factor (MyD) 88, thus providing a molecular basis for the selective activation of HIF-1 in differentiated THP-1 cells.
Databáze: OpenAIRE
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