Calcium signaling restitution prevents T-cell proliferative suppression by prostaglandin E2.
Previous studies from our laboratory have implicated a role for Ca2+ in prostaglandin E2 (PGE2)-induced suppression in T-cell proliferation during sepsis. The present study further elucidated the mechanism of PGE2-induced suppression in T-cell proliferation. We assessed whether prevention of the suppression in Ca2+ mobilization in PGE2-treated T-cells would restore proliferation. Rat splenic T-cell Ca2+ mobilization and proliferation were measured after stimulation of cells with concanavalin A (Con A) employing Fura-2 spectroscopy and cellular [3H]thymidine uptake techniques, respectively. PGE2 and other agents that directly up-regulate the PGE2-mediated cell signaling events (e.g., cholera toxin and forskolin), substantially suppressed both Con A-induced proliferation (p < .01) and Ca2+ mobilization in T-cells (p < .01). When stimulated with Con A plus ionomycin, [Ca2+]i in PGE2 treated T-cells (395 +/- 21, nM) was not significantly different (p > .05) from that observed in Con A-stimulated T-cells without the PGE2 exposure (351 +/- 8.6). The stimulation of PGE2-treated T-cells with ionomycin and Con A also significantly (p < .025), if not completely, prevented the PGE2-induced suppression in T-cell proliferation. These results suggest that the cross-talk between the TCR- and PGE2-mediated signaling in T-cells negatively modulates the TCR signals at the Ca2+ mobilization step and/or earlier to it.
Choudhry
M A
MA
Department of Physiology, Stritch School of Medicine, Loyola University Chicago, Maywood, Illinois 60153, USA.
Sayeed
M M
MM
D000818:Animals; D002118:Calcium / Q000502:physiology*; D003208:Concanavalin A / Q000494:pharmacology; D000242:Cyclic AMP / Q000502:physiology; D015232:Dinoprostone / Q000494:pharmacology*; D015759:Ionomycin / Q000494:pharmacology; D007476:Ionophores / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D011948:Receptors, Antigen, T-Cell / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology*; D013154:Spleen / Q000166:cytology / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000187:drug effects*
D007476:Ionophores; D011948:Receptors, Antigen, T-Cell; D003208:Concanavalin A; D015759:Ionomycin; D000242:Cyclic AMP; D015232:Dinoprostone; D002118:Calcium