PGE₂suppresses mitogen-induced Ca²⁺mobilization in T cells

Abstract

PGE2-mediated suppression of T cell proliferation during sepsis could result from altered Ca2+ signaling. The present study evaluated the effects of PGE2 on Ca2+ release from intracellular stores and its influx through the plasma membrane in splenic T cells from Sprague-Dawley rats. Intracellular Ca2+ concentration ([Ca2+]i) responses in individual T cells were assessed using the Ca2+ imaging technique, and the release of Ca2+ from intracellular stores and Ca2+ influx were spectrofluorometrically quantified in T cell suspensions. Under unstimulated conditions, nearly 85% of T cells exhibited [Ca2+]i </=50 nM. After stimulation with concanavalin A (Con A), an increase in [Ca2+]i was recorded in approximately 60% of the cells. The pretreatment of T cells with PGE2 had no apparent effect on [Ca2+]i in resting cells; it significantly suppressed the Con A-induced increase in [Ca2+]i in all of the Con A-responsive cells. Ca2+ release from the intracellular stores contributed to the early spike in [Ca2+]i, and the late phase of elevation in [Ca2+]i was dependent on Ca2+ influx through the plasma membrane. Our data suggest that PGE(2) causes an overall suppression of the Con A-induced [Ca2+]i elevation in T cells via inhibiting both Ca2+ influx and its release from the intracellular stores.

Corticosterone suppresses mesenteric lymph node T cells by inhibiting p38/ERK pathway and promotes bacterial translocation after alcohol and burn injury

“…Thus the suppression in p38 and ERK1/2 is likely to play a major role in Cort-mediated suppression of T cell proliferations and IL-2 production after a combined insult of EtOH intoxication and burn injury. Previous studies from our laboratory and others have shown that T cell dysfunction during burn and sepsis is accompanied with alterations in P59 fyn kinase activity, PKC, and Ca 2ϩ signaling (7,8,9,12,25). Because the activation of P59 fyn and Ca 2ϩ signaling precedes p38 and ERK1/2 activation, alterations in either of these pathways may potentially contribute to a suppression of p38 and ERK1/2 in T cells in EtOH and burn injury.…”

“…fyn , which phosphorylate Zap-70 (7,9,12,17,26). ZAP-70 then phosphorylates phospholipase C-␥ (PLC-␥) to hydrolyze phosphatidylinositol 4,5-bisphosphate into D-myoinositol 1,4,5-trisphosphate [Ins(1,4,5)P 3 ] and diacylglycerol (DAG).…”

Prostaglandin E2 Induces FOXP3 Gene Expression and T Regulatory Cell Function in Human CD4+ T Cells

“…Previous studies have focused on the direct effect of PGE 2 in mediating suppression of lymphocyte proliferation, highlighting the role of calcium-dependent mechanisms (29,30). In the current study we first investigated whether exogenous PGE 2 was able to augment the suppressive activity of CD4 ϩ CD25 ϩ T reg cells.…”

Cycloxygenase-2 Inhibition Augments the Efficacy of a Cancer Vaccine

“…18,19). PGE 2 has been shown to inhibit T-cell proliferation by altering polyamine synthesis (20), inhibiting intracellular calcium release (21), and inhibiting p59 protein tyrosine kinase (22). PGE 2 profoundly inhibited IFN-g and IL-2 production (23) while enhancing IL-4 and IL-10 production (24), thereby promoting a Th2 response over a Th1 antitumor response.…”