Activation of human monocytes by LPS and DHEA.
Dehydroepiandrosterone (DHEA) alone, whatever the concentration used, or lipopolysaccharide (LPS) alone at 0.2 ng/ml did not induce the release of interleukin-6 (IL-6) or tumor necrosis factor (TNF) by human monocytes. However DHEA (10[-9] M or 10[-12] M) in association with LPS (0.2 ng/ml) did induce the release of IL-6 and TNF. When human monocytes were activated by 1 microg/ml LPS, both IL-6 and TNF secretions were observed. Monocytes activated by both DHEA (10[-9] M or 1O[-12] M) and LPS (1 microg/ml) secreted IL-6 and TNF at a higher level than that observed for monocytes activated only by LPS (1 microg/ml) alone. DHEA alone, whatever the concentration used, or LPS alone at 0.2 ng/ml did not induce the activation of mitogen-activated protein kinases (MAPkinases) and protein kinase C (PKC) or the expression of c-fos and c-jun. However DHEA (10[-9] M or 10[-12] M) and 0.2 ng/ml LPS together induced the activation of both MAPKinases and PKC and the expression of c-fos and c-jun. Furthermore, the activation of PKC and MAPKinases and the expression of c-fos and c-jun were much greater when human monocytes were activated by both LPS (1 microg/ml) and DHEA (10[-9] M or 10[-12] M) than when the monocytes were activated only by LPS at 1 microg/ml. Therefore, DHEA and LPS displayed a synergistic effect on monocyte activation.
Delpedro
A D
AD
Unité INSERM 294, Laboratoire d'Hématologie et d'Immunologie CHU Xavier Bichat, Paris, France.
Barjavel
M J
MJ
Mamdouh
Z
Z
Bakouche
O
O
D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D003687:Dehydroepiandrosterone / Q000494:pharmacology*; D004357:Drug Synergism; D004789:Enzyme Activation; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D009000:Monocytes / Q000187:drug effects*; D011493:Protein Kinase C / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis; D016755:Proto-Oncogene Proteins c-jun / Q000096:biosynthesis; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D015850:Interleukin-6; D008070:Lipopolysaccharides; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D014409:Tumor Necrosis Factor-alpha; D003687:Dehydroepiandrosterone; D011493:Protein Kinase C; D017871:Calcium-Calmodulin-Dependent Protein Kinases