Human recombinant C5a enhances lipopolysaccharide-induced synthesis of interleukin-6 by human monocytes.
The effect of human recombinant C5a (hrC5a) on the synthesis of interleukin-6 (IL-6) was studied in human monocytes. Monocytes incubated in the absence of hrC5a and of bacterial lipopolysaccharide (LPS) produced only low amounts (less than 100 U/2 x 10(6) cells/16 h) of IL-6 activity. LPS in concentrations from 10 pg ml-1 to 10 ng ml-1 greatly stimulated the synthesis of IL-6 to about 50.000 U/10(6) cells/16 h. When hrC5a was added to the monocyte media maximal IL-6 synthesis was reached at lower LPS concentrations, i.e. at 0.1 ng ml-1 LPS in the presence of 100 ng ml-1 hrC5a. Maximal IL-6 production was not significantly enhanced by hrC5a. Metabolic labelling with [35S]-methionine followed by immunoprecipitation of IL-6 showed that the increased IL-6 activity in the medium of hrC5a treated monocytes was due to a stimulation of the de novo synthesis of IL-6. Increased amounts of IL-6 mRNA were found in monocytes treated with LPS and hrC5a compared with monocytes stimulated only with LPS. HrC5a prolonged the elevation of IL-6 mRNA levels after stimulation of monocytes with LPS. HrC5a thus enhanced the LPS-induced synthesis of IL-6 by human monocytes.
Gross
V
V
Medizinische Universitätsklinik, Freiburg, Germany.
Andus
T
T
D002478:Cells, Cultured; D015936:Complement C5a / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D015850:Interleukin-6 / Q000096:biosynthesis*; D008070:Lipopolysaccharides / Q000008:administration & dosage / Q000276:immunology; D009000:Monocytes / Q000276:immunology*; D012333:RNA, Messenger / Q000378:metabolism
D015850:Interleukin-6; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D015936:Complement C5a