Prostaglandin E-2 induces interleukin-8 gene transcription by activating C/EBP homologous protein in human T lymphocytes

The effect of prostaglandin E2 (PGE2) in regulating the synthesis of the pro-inflammatory chemokine inter-leukin-8 (IL-8) in T lymphocytes is not yet defined, even though it may reduce or enhance IL-8 synthesis in other cell types. Here, we demonstrate that, in human T cells, PGE2 induced IL-8 mRNA transcription through prostaglandin E2 receptors 1- and 4-dependent signal transduction pathways leading to the activation of the transcription factor C/EBP homologous protein (CHOP), never before implicated in IL-8 transcription. Several kinases, including protein kinase C, Src family tyrosine kinases, phosphatidylinositol 3-kinase, and p38 MAPK, were involved in PGE2-induced CHOP activation and IL-8 production. The transactivation of the IL-8 promoter by CHOP was NF-κB-independent. Our data suggest that PGE2 acts as a potent pro-inflammatory mediator by inducing IL-8 gene transcription in activated T cells through different signal transduction pathways leading to CHOP activation. These findings show the complexity with which PGE2 regulates IL-8 synthesis by inhibiting or enhancing its production depending on the cell types and environmental conditions.