Prostaglandin E₂ and the increase of intracellular cAMP inhibit the expression of interleukin 2 receptors in human T cells

Abstract

We have analyzed the effect mediated by prostaglandin E2 (PGE2) and different reagents that increase intracellular cAMP on the expression of the p55 subunit (CD25) of interleukin 2 receptors (IL 2R), on the levels of CD25-specific mRNA and on the expression of high affinity IL 2R. In purified T cells, activated either by an anti-CD3 monoclonal antibody or phytohemagglutinin, the addition of PGE2 (10(-6) M), forskolin (5 X 10(-5) M), cholera toxin (0.2 microgram/ml) or dibutyryl cAMP (dBcAMP) (10(-4) M) decreased the cell surface expression of IL 2R by reducing (40%-78% inhibition) the proportions of CD25+ cells as well as the expression of high affinity IL 2R, detectable after 24 h. Furthermore, it was observed that PGE2 reduced the concentration of IL 2R-specific mRNA after a 6-h period of activation, indicating that its regulatory activity takes place at a pretranslational level. The addition of exogenous recombinant IL 2 only partially reversed the inhibition, thus suggesting that PGE2 and increased intracellular concentration of cAMP directly interfered with CD25 expression and that their effect could not be merely attributed to a lack of IL 2-dependent positive feedback. Cells cultured under the same conditions in the presence of phorbol myristate acetate, that activates protein kinase C, were refractory to the cAMP-mediated regulation. Finally, we demonstrate that both PGE2 and dBcAMP inhibit the generation of inositol metabolites after T cell activation, thus indicating that these reagents interfere with early signal transduction mechanisms which precede the synthesis of IL 2R.

Sex differences and estrogen modulation of the cellular immune response after injury

“…Prostaglandins have long been shown to play a pivotal role in mediating the cellular immune response following trauma and burn injury. Increased circulating levels of PGE 2 inhibit T-cell mitogenesis, macrophage antigen presentation, and phagocytosis [66][67][68] that may ultimately lead to a poor clinical outcome in burned mice and humans. In the mouse model of burn injury, there was a 4-fold increase in PGE 2 production by LPS-stimulated macrophages from burn-injured females compared to sham-treated controls at 10 days post injury, as shown by Gregory et al [69].…”

Posttranscriptional Downregulation of c-IAP2 by the Ubiquitin Protein Ligase c-IAP1 In Vivo

“…following the manufacturer's recommended protocol. RNA (15 g) was examined by Northern blotting as previously described (29). Specific cDNA probes for c-IAP2 mRNA and GAPDH mRNA were labeled with [␣- 32 P]dCTP by the use of a random primer kit (Stratagene).…”

Adenylate cycalse toxin ofBordetella pertussisinhibits TLR-induced IRF-1 and IRF-8 activation and IL-12 production and enhances IL-10 through MAPK activation in dendritic cells

“…6C) and did not affect suppression of IL-12p70 by CyaA (data not shown). PGE2 has previously been shown to stimulate cAMP production in various cell types [30,31]. Therefore, we examined the possibility that PGE2 might mimic the effects of CyaA.…”