Title : PGE2 enhanced TNF╬▒-mediated IL-8 induction in monocytic cell lines and PBMC.

Pub. Date : 2019 Jan

PMID : 29929938






11 Functional Relationships(s)
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1 PGE2 enhanced TNFalpha-mediated IL-8 induction in monocytic cell lines and PBMC. Dinoprostone C-X-C motif chemokine ligand 8 Homo sapiens
2 BACKGROUND & PURPOSE: Recent studies suggested a role of prostaglandin E2 (PGE2) in the expression of the chemokine IL-8 by monocytes. Dinoprostone C-X-C motif chemokine ligand 8 Homo sapiens
3 BACKGROUND & PURPOSE: Recent studies suggested a role of prostaglandin E2 (PGE2) in the expression of the chemokine IL-8 by monocytes. Dinoprostone C-X-C motif chemokine ligand 8 Homo sapiens
4 KEY RESULTS: In monocytic cell lines THP-1, MonoMac and U937 PGE2 had only a marginal impact on IL-8 induction but strongly enhanced TNFalpha-induced IL-8 mRNA and protein synthesis. Dinoprostone C-X-C motif chemokine ligand 8 Homo sapiens
5 KEY RESULTS: In monocytic cell lines THP-1, MonoMac and U937 PGE2 had only a marginal impact on IL-8 induction but strongly enhanced TNFalpha-induced IL-8 mRNA and protein synthesis. Dinoprostone C-X-C motif chemokine ligand 8 Homo sapiens
6 Similarly, in PBMC IL-8 mRNA induction was larger by simultaneous stimulation with TNFalpha and PGE2 than by either stimulus alone. Dinoprostone C-X-C motif chemokine ligand 8 Homo sapiens
7 In HEK293 cells expressing EP4, but not in wild type HEK293 cells lacking EP4, PGE2 enhanced TNFalpha-induced IL-8 protein and mRNA synthesis. Dinoprostone C-X-C motif chemokine ligand 8 Homo sapiens
8 In THP-1 cells, the enhancement of TNFalpha-mediated IL-8 mRNA induction by PGE2 was mimicked by a PKA-activator. Dinoprostone C-X-C motif chemokine ligand 8 Homo sapiens
9 PGE2 and TNFalpha synergistically activated transcription factor CREB, induced C/EBPss expression and enhanced the activity of an IL-8 promoter fragment containing -223 bp upstream of the transcription start site. Dinoprostone C-X-C motif chemokine ligand 8 Homo sapiens
10 CONCLUSIONS AND IMPLICATIONS: These findings suggest that a combined stimulation of TNFalpha and PGE2/EP4 signal chains in monocytic cells leads to maximal IL-8 promoter activity, as well as IL-8 mRNA and protein induction, by activating the PKA/CREB/C/EBPss as well as NF-kappaB signal chains. Dinoprostone C-X-C motif chemokine ligand 8 Homo sapiens
11 CONCLUSIONS AND IMPLICATIONS: These findings suggest that a combined stimulation of TNFalpha and PGE2/EP4 signal chains in monocytic cells leads to maximal IL-8 promoter activity, as well as IL-8 mRNA and protein induction, by activating the PKA/CREB/C/EBPss as well as NF-kappaB signal chains. Dinoprostone C-X-C motif chemokine ligand 8 Homo sapiens