c-Jun N-terminal kinase is involved in mercuric ions-mediated interleukin-4 secretion in mast cells.
BACKGROUND
Interleukin (IL)-4 plays a prominent role in immune response. Mercuric compounds upregulate IL-4 expression in animal tissues, and this upregulation plays a role in mercuric-mediated immunomodulation. Mercuric ions-mediated IL-4 expression was observed in vitro in T lymphocytes and mast cells. In the present study, we investigated molecular mechanisms responsible for this effect of mercuric ions in mast cells.


METHODS
C1.MC/C57.1 mouse mast cells were exposed in vitro to increasing concentrations of Hg(2+) in the absence or presence of the specific c-Jun N-terminal kinase (JNK) inhibitor SP600125. The level of phosphorylated c-Jun in mast cells was determined by Western blotting, JNK activity assessed with in vitro kinase assay and the amount of secreted IL-4 determined by ELISA.


RESULTS
We observed that Hg(2+) upregulated c-Jun phosphorylation on Ser 73 at concentrations which overlapped concentrations mediating IL-4 secretion. Phosphorylation of c-Jun in mast cells was associated with an increase in JNK activity. The specific JNK inhibitor SP600125 abolished both mercuric-induced c-Jun phosphorylation and IL-4 secretion in mast cells.


CONCLUSIONS
These observations are consistent with the hypothesis that JNK is one of the signaling proteins mediating the effect of Hg(2+) on IL-4 expression in mast cells and is engaged in environmentally mediated immunomodulation.
Walczak-Drzewiecka
Aurelia
A
Centre for Medical Biology, Polish Academy of Sciences, Lodz, Poland.
Wyczółkowska
Janina
J
Dastych
Jarosław
J
D000818:Animals; D000873:Anthracenes / Q000494:pharmacology; D018929:Cell Culture Techniques; D015847:Interleukin-4 / Q000096:biosynthesis / Q000276:immunology*; D007477:Ions / Q000276:immunology; D048031:JNK Mitogen-Activated Protein Kinases / Q000187:drug effects / Q000276:immunology*; D008407:Mast Cells / Q000187:drug effects / Q000276:immunology*; D008628:Mercury / Q000276:immunology*; D051379:Mice; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D015398:Signal Transduction; D015854:Up-Regulation
D000873:Anthracenes; D007477:Ions; D047428:Protein Kinase Inhibitors; C432165:pyrazolanthrone; D015847:Interleukin-4; D048031:JNK Mitogen-Activated Protein Kinases; D008628:Mercury