Cristin-resultat-ID: 365341
Sist endret: 25. oktober 2016 14:34
NVI-rapporteringsår: 2008
Resultat
Vitenskapelig artikkel
2008

Fluoride-induced IL-8 release in human epithelial lung cells: Relationship to EGF-receptor-, SRC- and MAP-kinase activation

Bidragsytere:
  • Magne Refsnes
  • Tonje S. Skuland
  • Per E. Schwarze
  • Johan Øvrevik og
  • Marit Låg

Tidsskrift

Toxicology and Applied Pharmacology
ISSN 0041-008X
e-ISSN 1096-0333
NVI-nivå 2

Om resultatet

Vitenskapelig artikkel
Publiseringsår: 2008
Volum: 227
Hefte: 1
Sider: 56 - 67

Importkilder

Isi-ID: 000253222600007

Beskrivelse Beskrivelse

Tittel

Fluoride-induced IL-8 release in human epithelial lung cells: Relationship to EGF-receptor-, SRC- and MAP-kinase activation

Sammendrag

Exposure of human epithelial lung cells to fluorides is known to induce a marked increase in the release of interleukin (IL)-8, a chemokine involved in neutrophil recruitment. In the present study, the involvement of mitogen-activating protein kinases (MAPKs), the role of upstream activation of Src family kinases (SFKs), epidermal growth factor receptor (EGFR) activation and the interrelationships between these pathways in fluoride-induced IL-8 were examined in a human epithelial lung cell line (A549). Sodium fluoride strongly activated MAPK, in particular JNK1/2 and p38. The ERK1/2-inhibitor PD98059, the p38-inhibitor SB202190 and the JNK1/2-inhibitor SP600125 partially inhibited the fluoride-induced IL-8 response. Combinations of these inhibitors reduced the responses nearly to basal levels. Treatment with siRNA against JNK2 also reduced the IL-8 response to fluoride. Furthermore, fluoride activated SFKs, which was abolished by the SFK-inhibitor PP2. PP2 substantially inhibited the increased levels of IL-8, and partially reduced the fluoride-induced activation of ERK1/2, p38 and JNK1/2. Fluoride exposure also led to a phosphorylation of the EGFR, that was partially inhibited by PP2. AG1478, an EGFR-inhibitor, partially reduced the fluoride-induced IL-8 response and the phosphorylation of JNK1/2 and ERK1/2, but less the phosphorylation of p38. The effects of AG1478 were less than that of PP2. In conclusion, our findings suggest that the fluoride-induced IL-8 release involves the combined activation of ERK1/2, JNK1/2 and p38, and that the phosphorylation of these kinases, and in particular JNK1/2 and ERK1/2, partly, is mediated via a SFK-dependent EGFR-linked pathway. SFK-dependent, but EGFR-independent mechanisms seem important, and especially for phosphorylation of p38.

Bidragsytere

Magne Arnold Refsnes

Bidragsyterens navn vises på dette resultatet som Magne Refsnes
  • Tilknyttet:
    Forfatter
    ved Avdeling for luft og støy ved Folkehelseinstituttet

Tonje Schwach Skuland

Bidragsyterens navn vises på dette resultatet som Tonje S. Skuland
  • Tilknyttet:
    Forfatter
    ved Avdeling for luft og støy ved Folkehelseinstituttet

Per Everhard Schwarze

Bidragsyterens navn vises på dette resultatet som Per E. Schwarze
  • Tilknyttet:
    Forfatter
    ved Avdeling for luft og støy ved Folkehelseinstituttet

Johan Øvrevik

  • Tilknyttet:
    Forfatter
    ved Avdeling for luft og støy ved Folkehelseinstituttet

Marit Låg

  • Tilknyttet:
    Forfatter
    ved Avdeling for luft og støy ved Folkehelseinstituttet
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