Journal article
Activation of nuclear factor kappa B by diesel exhaust particles in mouse epidermal cells through phosphatidylinositol 3-kinase/Akt signaling pathway
Biochemical pharmacology, Vol.67(10), pp.1975-1983
2004
DOI: 10.1016/j.bcp.2004.01.023
PMID: 15130773
Abstract
Diesel exhaust particles (DEP) induce intense inflammatory and allergic immune responses. The epidermal cells receive much exposure to DEP, and are an important source of pro-inflammatory cytokines and other inflammatory mediators. Transcription factors, such as nuclear factor kappa B (NF-κB) and activator protein 1 (AP-1), regulate the expression of these mediators. We hypothesize that the transcription factors are target of DEP action. The current study sought to determine whether DEP-activated NF-κB and AP-1 in a mouse epidermal cell line, JB6 P
+ cells. Using stable transfectants of JB6 P
+ cells expressing NF-κB or AP-1 luciferase reporter constructs, we demonstrated that exposure to DEP at a non-cytotoxic concentration significantly enhanced the transactivation of NF-κB, but not AP-1. Furthermore, DEP promoted phosphorylation of Akt, a substrate of phosphatidylinositol 3-kinase (PI3K), on Ser-473 and Thr-308 in a PI3K-dependent manner, and enhanced phosphorylation of down-stream p70/p85 S6 kinases (p70/p85S6K) as well as glycogen synthase kinase-3β (GSK-3β). Blockage of PI3K activation eliminated DEP-stimulated NF-κB transactivation. Although SAPK/JNK pathway was modestly activated by DEP, it was not involved in NF-κB transactivation. DEP had little effect on the phosphorylation of ERKs and p38 MAPK. Thus, DEP-induced transactivation of NF-κB is mediated by PI3K/Akt signaling pathway.
Details
- Title: Subtitle
- Activation of nuclear factor kappa B by diesel exhaust particles in mouse epidermal cells through phosphatidylinositol 3-kinase/Akt signaling pathway
- Creators
- Cuiling Ma - West Virginia UniversityJin Wang - Albert Einstein College of MedicineJia Luo - West Virginia University
- Resource Type
- Journal article
- Publication Details
- Biochemical pharmacology, Vol.67(10), pp.1975-1983
- Publisher
- Elsevier Inc
- DOI
- 10.1016/j.bcp.2004.01.023
- PMID
- 15130773
- ISSN
- 0006-2952
- eISSN
- 1873-2968
- Language
- English
- Date published
- 2004
- Academic Unit
- Pathology
- Record Identifier
- 9984186571302771
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