Effect of prostaglandin E2 on PMA-induced macrophage differentiation.
Major trauma such as severe bums and extensive surgery could result in accelerated macrophage differentiation and hyperactivation causing an excessive release of proinflammatory cytokines and prostaglandin E2 (PGE2) with consequent severe impairment of immunologic reactivity. HL-60 cells stimulated with phorbol 12-myristate 13-acetate (PMA) have been used as a model to asses the PGE2 role in the macrophage differentiation observed after major trauma. Cell adhesion, matrix metalloproteinase-9 (MMP-9) and tumor necrosis factor-alpha (TNF-alpha) production were measured after 24 h of PMA treatment in the presence of PGE2 (1 nM - 1 microM). PGE2 increased both the PMA-induced cell adhesion and MMP-9 production via EP2/EP4 receptors while it had no effect on the induced TNF-alpha release. The cAMP/PKA pathway, usually linked to EP2/EP4 activation, was not involved in the phenomenon, suggesting that an alternative signalling pathway could be linked to a PKC-activated enzyme. In fact PGE2 activity was partially inhibited by Wortmannin, a phosphoinositide-3 kinase (PI-3K) inhibitor indicating that PGE2 act as a co-factor able to increase macrophage differentiation in vitro via a PI-3K dependent pathway that could be also involved in the immunosuppression observed in the aftermath of trauma.
Renò
Filippo
F
Human Anatomy Laboratory, Medical Sciences Department, University of Eastern Piedmont A. Avogadro, Via Solaroli 17, 28100 Novara, Italy.
Cannas
Mario
M
D002448:Cell Adhesion / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects*; D005576:Colforsin / Q000494:pharmacology; D015232:Dinoprostone / Q000494:pharmacology*; D018922:HL-60 Cells; D006801:Humans; D008264:Macrophages / Q000166:cytology* / Q000187:drug effects; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D014409:Tumor Necrosis Factor-alpha; D005576:Colforsin; D020780:Matrix Metalloproteinase 9; D015232:Dinoprostone; D013755:Tetradecanoylphorbol Acetate