C-Jun N-Terminal Kinase Is Involved in Mercuric Ions-Mediated Interleukin-4 Secretion in Mast Cells

Abstract

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 Hg²⁺ 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 Hg²⁺ 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 Hg²⁺ on IL-4 expression in mast cells and is engaged in environmentally mediated immunomodulation.