Human interleukin-6 acts as a co-factor for the up-regulation of C3 production by rat liver epithelial cells.
We investigated the role of human interleukin-6 (IL-6) in the regulation of the third component of complement (C3) biosynthesis by cultured rat liver epithelial cells. A natural human IL-6 (nh IL-6) preparation was shown to up-regulate C3 production, whereas an Escherichia coli-derived recombinant human IL-6 (rh IL-6) displayed no activity on C3 biosynthesis. However, the C3-stimulating activity of the nh IL-6 preparation was only partially reduced when treated with an antihuman IL-6 monoclonal antibody. Binding studies indicated that although it was devoid of any C3 stimulating activity, rh IL-6 specifically bound to hepatic cell receptors (Kd = 0.38 nM) and possessed the same binding affinity as nh IL-6. Furthermore, the substitution of natural IL-6 molecules for the recombinant IL-6 led to the recovery of the initial C3-stimulating activity. These studies demonstrated that human IL-6 alone does not stimulate rat liver epithelial cell C3 production but is able to accentuate the C3-stimulating activity of unrecognized components which are present in the nh IL-6 preparation. Human IL-6 thus appears to act as a co-factor for the up-regulation of hepatic C3 production.
Laboratoire de Biochimie Médicale, Hôpital d'Enfants, Dijon, France.
D
D
Platel
M
M
Guiguet
F
F
Briere
A
A
Bernard
G
G
Mack
D000818:Animals; D002460:Cell Line; D003176:Complement C3 / Q000096:biosynthesis*; D004847:Epithelial Cells; D004848:Epithelium / Q000378:metabolism; D006801:Humans; D015850:Interleukin-6 / Q000502:physiology*; D008099:Liver / Q000166:cytology / Q000378:metabolism*; D051381:Rats; D015854:Up-Regulation
D003176:Complement C3; D015850:Interleukin-6