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NADPH oxidase inhibitor diphenyliodonium abolishes lipopolysaccharide‐induced down‐regulation of transferrin receptor expression in N2a and BV‐2 cells
Author(s) -
Reis Katarina,
Hälldin Jonas,
Fernaeus Sandra,
Pettersson Christina,
Land Tiit
Publication year - 2006
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.21005
Subject(s) - nadph oxidase , transferrin receptor , tlr4 , chemistry , apocynin , lipopolysaccharide , microbiology and biotechnology , ferritin , nitric oxide , nitric oxide synthase , signal transduction , receptor , reactive oxygen species , biology , biochemistry , immunology , organic chemistry
The activation of cellular inflammatory response is tightly linked to induced production of reactive oxygen species (ROS) and nitric oxide (NO), which in turn have been identified as important regulators of cellular iron metabolism. In the present study, we have used the microglia cell line BV‐2 and the neuroblastoma cell line N2a to study the regulatory effects of the microbial agent lipopolysaccharide (LPS) on the expression of the transferrin receptor (TfR) and ferritin in cell lines with different characteristics. The receptor mainly responsible for LPS recognition is the Toll‐like receptor 4 (TLR4) that triggers a variety of intracellular signalling cascades leading to the induction of transcription of target genes involved in the innate immune response. Among the pathways to be activated is the MAPK cascade leading to the activation of nuclear factor‐κB that induces transcription of a variety of genes, e.g., inducible nitric oxide synthase (iNOS). The TLR4‐mediated LPS response also induces the production of ROS through a mechanism(s) suggested to involve the activation of NADPH oxidase(s). This study shows that exposure of BV‐2 and N2a cells to LPS results in decreased TfR protein levels and increased H‐ferritin mRNA levels. The LPS down‐regulatory effect on TfR protein expression is abolished by the NADPH oxidase inhibitor diphenyliodonium (DPI) but is not affected by the free radical scavenger N‐acetyl‐L‐cysteine (NAC) or the iNOS inhibitor aminoguanidine (AG). The increased H‐ferritin mRNA levels in response to LPS are not affected by DPI, NAC, or AG. © 2006 Wiley‐Liss, Inc.