Mercuric chloride stimulates distinct signal transduction pathway for DNA synthesis in a T-cell line, CTLL-2.
Exposure of an interleukin-2 (IL-2)-dependent murine T-cell line (CTLL-2) to mercuric chloride in in vitro culture induced a low but definite level of DNA synthesis in the absence of exogenous IL-2, and further enhanced the IL-2-induced DNA synthesis. Addition of anti-IL-2 or anti-IL-4 antibody to the culture, which neutralized all of the IL-2 or IL-4 activity, respectively, never inhibited the mercuric chloride-mediated DNA synthesis. Correspondingly, no detectable level of IL-2, IL-4, and IL-15 mRNA was found in mercuric chloride-treated CTLL-2 cells in our test condition. Stimulation of CTLL-2 cells with IL-2 induced phosphorylation on extracellular signal-regulated kinases more intensively than on c-Jun NH2-terminal kinases (JNKs), and provoked tyrosine phosphorylation of Janus kinases (JAKs) and signal transducers and activators of transcription (STATs). In contrast, by mercuric chloride stimulation, JNKs and c-Jun were preferentially phosphorylated, but no detectable level of phosphorylation was induced on JAKs and STATs. These findings provided a possibility that mercuric chloride promoted lymphocyte proliferation through a JNK-linked signal cascade in CTLL-2 cells, which differs from that triggered by IL-2.
Du
J
J
Department of Immunology, Nagoya University School of Medicine, Aichi, Japan.
Suzuki
H
H
Nagase
F
F
Akhand
A A
AA
Yokoyama
T
T
Nakashima
I
I
D000818:Animals; D015153:Blotting, Western; D004247:DNA / Q000096:biosynthesis*; D017931:DNA Primers / Q000737:chemistry; D004261:DNA Replication / Q000187:drug effects; D005434:Flow Cytometry / Q000379:methods; D007376:Interleukin-2 / Q000494:pharmacology; D048031:JNK Mitogen-Activated Protein Kinases; D008213:Lymphocyte Activation / Q000187:drug effects; D048670:MAP Kinase Kinase 4; D008627:Mercuric Chloride / Q000494:pharmacology*; D051379:Mice; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism; D010766:Phosphorylation; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects*; D013601:T-Lymphocytes / Q000187:drug effects / Q000378:metabolism*; D014443:Tyrosine / Q000378:metabolism
D017931:DNA Primers; D007376:Interleukin-2; D016755:Proto-Oncogene Proteins c-jun; D012333:RNA, Messenger; D014443:Tyrosine; D008627:Mercuric Chloride; D004247:DNA; D048031:JNK Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4; D020929:Mitogen-Activated Protein Kinase Kinases