HgCl2-induced interleukin-4 gene expression in T cells involves a protein kinase C-dependent calcium influx through L-type calcium channels.
Mercuric chloride (HgCl2) induces T helper 2 (Th2) autoreactive anti-class II T cells in Brown Norway rats. These cells produce interleukin (IL)-4 and induce a B cell polyclonal activation that is responsible for autoimmune disease. In Brown Norway rats, HgCl2 triggers early IL-4 mRNA expression both in vivo and in vitro by T cells, which may explain why autoreactive anti-class II T cells acquire a Th2 phenotype. The aim of this study was to explore the transduction pathways by which this chemical operates. By using two murine T cell hybridomas that express IL-4 mRNA upon stimulation with HgCl2, we demonstrate that: 1) HgCl2 acts at the transcriptional level without requiring de novo protein synthesis; 2) HgCl2 induces a protein kinase C-dependent Ca2+ influx through L-type calcium channels; 3) calcium/calcineurin-dependent pathway and protein kinase C activation are both implicated in HgCl2-induced IL-4 gene expression; and 4) HgCl2 can activate directly protein kinase C, which might be one of the main intracellular target for HgCl2. These data are in agreement with an effect of HgCl2 which is independent of antigen-specific recognition. It may explain the T cell polyclonal activation in the mercury model and the expansion of pathogenic autoreactive anti-class II Th2 cells in this context.
Badou
A
A
INSERM Unité 28, Institut Fédératif de Recherche 30, Hôpital Purpan Place du Dr. Baylac, Toulouse 31059 cedex, France. Abdellah.Badou@purpan.inserm.fr
Savignac
M
M
Moreau
M
M
Leclerc
C
C
Pasquier
R
R
Druet
P
P
Pelletier
L
L
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000378:metabolism*; D002474:Cell-Free System; D004789:Enzyme Activation; D005786:Gene Expression Regulation / Q000187:drug effects*; D006825:Hybridomas; D015847:Interleukin-4 / Q000235:genetics*; D017136:Ion Transport; D008627:Mercuric Chloride / Q000494:pharmacology*; D011493:Protein Kinase C / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D013601:T-Lymphocytes / Q000378:metabolism*
D015220:Calcium Channels; D012333:RNA, Messenger; D015847:Interleukin-4; D008627:Mercuric Chloride; D011493:Protein Kinase C; D002118:Calcium