Prostaglandin E2 induces interleukin-8 gene transcription by activating C/EBP homologous protein in human T lymphocytes.
The effect of prostaglandin E(2) (PGE(2)) in regulating the synthesis of the pro-inflammatory chemokine interleukin-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, PGE(2) induced IL-8 mRNA transcription through prostaglandin E(2) 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 PGE(2)-induced CHOP activation and IL-8 production. The transactivation of the IL-8 promoter by CHOP was NF-kappaB-independent. Our data suggest that PGE(2) 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 PGE(2) regulates IL-8 synthesis by inhibiting or enhancing its production depending on the cell types and environmental conditions.
Caristi
Silvana
S
Department of Experimental Pathology and Microbiology, University of Messina, 98125 Messina, Italy.
Piraino
Giovanna
G
Cucinotta
Maria
M
Valenti
Andrea
A
Loddo
Saverio
S
Teti
Diana
D
D000328:Adult; D015153:Blotting, Western; D022762:CCAAT-Enhancer-Binding Proteins / Q000378:metabolism*; D018106:CD28 Antigens / Q000096:biosynthesis; D003720:Densitometry; D015232:Dinoprostone / Q000502:physiology*; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D007249:Inflammation; D016209:Interleukin-8 / Q000096:biosynthesis* / Q000378:metabolism; D019169:Jurkat Cells; D008213:Lymphocyte Activation; D008954:Models, Biological; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation; D011401:Promoter Regions, Genetic; D011493:Protein Kinase C / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D018078:Receptors, Prostaglandin E / Q000737:chemistry; D058306:Receptors, Prostaglandin E, EP1 Subtype; D058309:Receptors, Prostaglandin E, EP4 Subtype; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000378:metabolism*; D013997:Time Factors; D051742:Transcription Factor CHOP; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic; D014162:Transfection; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism; D019061:src-Family Kinases / Q000378:metabolism
D022762:CCAAT-Enhancer-Binding Proteins; D018106:CD28 Antigens; C497249:DDIT3 protein, human; D016209:Interleukin-8; C545635:PTGER1 protein, human; C545650:PTGER4 protein, human; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D018078:Receptors, Prostaglandin E; D058306:Receptors, Prostaglandin E, EP1 Subtype; D058309:Receptors, Prostaglandin E, EP4 Subtype; D014157:Transcription Factors; D051742:Transcription Factor CHOP; D019869:Phosphatidylinositol 3-Kinases; D019061:src-Family Kinases; D011493:Protein Kinase C; D048051:p38 Mitogen-Activated Protein Kinases; D015232:Dinoprostone