Role of calcium on interleukin-1 production by monocytes: its relevance during T cell proliferation.
T cell proliferation, in the presence of monocytes, triggered either by an anti-CD3 monoclonal antibody (mAb) or by a mitogenic pair of anti-CD2 mAbs was inhibited either by the calcium chelator EGTA or the calcium channel blocker nifedipin. Antibodies against interleukin-1 (IL-1) inhibited T cell proliferation in both mitogenic systems. However inhibition achieved by anti-IL-1 beta Ab was greater than by anti-IL-1 alpha Ab while the combination of both anti-rIL-1 alpha Ab + anti-rIL-1 beta could completely inhibit the CD3-triggered T cell proliferation. On the other hand, IL-1 production by LPS-stimulated monocytes was strongly decreased both by EGTA and nifedipin. Northern blot analysis showed that this inhibition paralleled a decrease of IL-1 alpha and beta messenger RNA (mRNA) expression only in the presence of EGTA but not in the presence of nifedipin. These results indicate that EGTA acted at the transcriptional level while nifedipin acted at a yet undefined posttranscriptional level. Thus, it is suggested that the impairment of T cell proliferation by calcium inhibitors could result not only from an effect on Ca2+ influx in T cells but also from interfering with the function of accessory cells, such as the production of IL-1.
Mahé
Y
Y
Laboratoire d'Immuno-Biologie Cellulaire, URA 1156 CNRS, Institut Gustave Roussy, Villejuif, France.
Wakasugi
H
H
Scamps
C
C
Chouaib
S
S
Tursz
T
T
D000911:Antibodies, Monoclonal; D015152:Blotting, Northern; D002118:Calcium / Q000502:physiology*; D002450:Cell Communication; D002478:Cells, Cultured; D015342:DNA Probes; D004305:Dose-Response Relationship, Drug; D004533:Egtazic Acid / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D007375:Interleukin-1 / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D007700:Kinetics; D008213:Lymphocyte Activation; D009000:Monocytes / Q000187:drug effects / Q000276:immunology*; D009543:Nifedipine / Q000494:pharmacology*; D012313:RNA / Q000235:genetics / Q000302:isolation & purification; D012333:RNA, Messenger / Q000235:genetics; D013601:T-Lymphocytes / Q000276:immunology*
D000911:Antibodies, Monoclonal; D015342:DNA Probes; D007375:Interleukin-1; D012333:RNA, Messenger; D004533:Egtazic Acid; D012313:RNA; D009543:Nifedipine; D002118:Calcium