ABSTRACT
In a previous study, we demonstrated that the length of glass fibers was a critical determinant of fiber potency in induction of tumor necrosis factor (TNF)-alpha and that activation of NF-kappaB was an important factor in this response. In the present study, we analyzed the role of mitogen-activated protein (MAP) kinases in the induction of TNF-alpha by glass fibers. Glass fibers induced phosphorylation of MAP kinases, p38, and ERK in primary rat alveolar macrophages, and this phosphorylation was associated with TNF-alpha gene expression. Long fibers were more potent than short fibers in activation of MAP kinases. Results from mechanistic analysis support that MAP kinases activate transcription factor c-Jun. The activated c-Jun acts on the TNF-alpha gene promoter through two binding sites, the cyclic AMP response element and the activator protein 1-binding site. These results suggest that in addition to the NF-kappaB pathway for TNF-alpha production, glass fibers are able to activate c-Jun through MAP kinase pathways that lead to induction of TNF-alpha expression.
Subject(s)
Glass , Macrophages, Alveolar/metabolism , Mitogen-Activated Protein Kinase 1/physiology , Mitogen-Activated Protein Kinases/physiology , Tumor Necrosis Factor-alpha/genetics , Animals , Cells, Cultured , Enzyme Inhibitors/pharmacology , Flavonoids/pharmacology , Genes, Reporter , Imidazoles/pharmacology , MAP Kinase Signaling System , Male , Mitogen-Activated Protein Kinase 1/antagonists & inhibitors , Mitogen-Activated Protein Kinase 1/metabolism , Mitogen-Activated Protein Kinase 3 , Mitogen-Activated Protein Kinases/antagonists & inhibitors , Mitogen-Activated Protein Kinases/metabolism , Promoter Regions, Genetic , Proto-Oncogene Proteins c-jun/metabolism , Pyridines/pharmacology , Rats , Rats, Sprague-Dawley , Response Elements , Transcription Factor AP-1/metabolism , Tumor Necrosis Factor-alpha/biosynthesis , p38 Mitogen-Activated Protein KinasesABSTRACT
This study used 15 beehives: five with Africanized queens sisters (Apis mellifera), five with Italian queens sisters (Apis mellifera ligustica), and five with Carniolan queens sisters (Apis meliifera carnica). The queens were fertilized naturally. This experiment was performed in the apiary of the Botucatu School of Veterinary Medicine and Animal Husbandry, UNESP, State of Säo Paulo, Brazil. The following data were obtained from the foraging bees: venom quantity in reservoir, 0.117ñ0.015, 0.139ñ0.020, and 0.147ñ0.024 (mg); venom quantity liberated in extraction apparatus, 0.073ñ0.012, 0.057ñ0.011 and 0.059ñ0.013 (mg); and sting electro stimulus threshold (volts), 10.75ñ1.37, 15.11ñ2.00, and 15.01ñ1.63 for Africanized, Italian x Africanized and Carniolan x Africanized, respectively. The Africanized honeybees possess less venom in reservoir than the European hybrids (Carniolan and Italian). However, they liberated a larger quantity of venom in the extraction apparatus and required lower electro stimulus threshold to promote stinging.
