Activation of mitogen-activated protein kinase p38 and extracellular signal-regulated kinase is involved in glass fiber-induced tumor necrosis factor-alpha production in macrophages

Citation
Jp. Ye et al., Activation of mitogen-activated protein kinase p38 and extracellular signal-regulated kinase is involved in glass fiber-induced tumor necrosis factor-alpha production in macrophages, J BIOL CHEM, 276(7), 2001, pp. 5360-5367
Citations number
35
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Biochemistry & Biophysics
Journal title
JOURNAL OF BIOLOGICAL CHEMISTRY
ISSN journal
0021-9258 → ACNP
Volume
276
Issue
7
Year of publication
2001
Pages
5360 - 5367
Database
ISI
SICI code
0021-9258(20010216)276:7<5360:AOMPKP>2.0.ZU;2-J
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 th is response. In the present study, we analyzed the role of mitogen-activate d protein (MAP) kinases in the induction of TNF-alpha by glass fibers. Glas s fibers induced phosphorylation of MAP kinases, p38, and ERK in primary ra t alveolar macrophages, and this phosphorylation was associated with TNF-al pha gene expression. Long fibers were more potent than short fibers in acti vation of MAP kinases. Results from mechanistic analysis support that MAP k inases 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 th at in addition to the NF-kappaB pathway for TNF-alpha production, glass fib ers are able to activate c-Jun through MAP kinase pathways that lead to ind uction of TNF-gamma expression.