title: Activation of nuclear factor kappa B by diesel exhaust particles in mouse epidermal cells through phosphatidylinositol 3-kinase/Akt signaling pathway.
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-kappaB) 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-kappaB and AP-1 in a mouse epidermal cell line, JB6 P(+) cells. Using stable transfectants of JB6 P(+) cells expressing NF-kappaB or AP-1 luciferase reporter constructs, we demonstrated that exposure to DEP at a non-cytotoxic concentration significantly enhanced the transactivation of NF-kappaB, 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-3beta (GSK-3beta). Blockage of PI3K activation eliminated DEP-stimulated NF-kappaB transactivation. Although SAPK/JNK pathway was modestly activated by DEP, it was not involved in NF-kappaB transactivation. DEP had little effect on the phosphorylation of ERKs and p38 MAPK. Thus, DEP-induced transactivation of NF-kappaB is mediated by PI3K/Akt signaling pathway.
authors.affiliation: Department of Microbiology, Immunology & Cell Biology, Robert C. Byrd Health Science Center, West Virginia University School of Medicine, Morgantown, WV 26506, USA.
authors.forename: Cuiling
authors.initials: C
authors.lastname: Ma
authors.forename: Jin
authors.initials: J
authors.lastname: Wang
authors.forename: Jia
authors.initials: J
authors.lastname: Luo
mesh_terms: D000818:Animals; D002460:Cell Line; D004817:Epidermis / Q000187:drug effects* / Q000201:enzymology; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D018808:Transcription Factor AP-1 / Q000378:metabolism; D001335:Vehicle Emissions / Q000633:toxicity*
chemical_list: D016328:NF-kappa B; D018808:Transcription Factor AP-1; D001335:Vehicle Emissions; D019869:Phosphatidylinositol 3-Kinases