Differential modulation of complement factor H and C3 expression by TNF-alpha in the rat. In vitro and in vivo studies.
The biosynthesis of alternative regulatory complement protein factor H was investigated using both an in vivo rat model and an in vitro rat hepatocyte culture system, and compared to that of C3 component. Subcutaneous injection of a single dose of 20 micrograms of recombinant murine tumor necrosis factor-alpha (rmTNF-alpha) had no effect on factor H liver mRNA levels, while it increased C3 mRNA levels. In correlation with this, serum factor H levels remained unchanged after rmTNF-alpha injection, whereas C3 levels were increased. In contrast in vitro studies showed that rmTNF-alpha had no effect on factor H and C3 expression by rat hepatocytes. Recombinant human interleukin-1 alpha (rhIL-1 alpha) did not alter the expression of factor H, whereas it increased C3 expression, and recombinant human interleukin-6 (rhIL-6) stimulated expression of both proteins. This study shows that TNF-alpha is not directly responsible for the increased levels of factor H observed in vivo during induced inflammation in the rat. Its in vivo effect on C3 secretion might be secondary to the TNF-alpha-induced release of IL-1 and/or IL-6.
Julen
N
N
INSERM Unité 78, Bois-Guillaume, France.
Davrinche
C
C
Ozanne
D
D
Lebreton
J P
JP
Fontaine
M
M
Ripoche
J
J
Daveau
M
M
D000818:Animals; D002478:Cells, Cultured; D003176:Complement C3 / Q000378:metabolism*; D003180:Complement C3b Inactivator Proteins / Q000378:metabolism*; D017242:Complement Factor H; D015870:Gene Expression / Q000187:drug effects; D066298:In Vitro Techniques; D007375:Interleukin-1 / Q000494:pharmacology; D015850:Interleukin-6 / Q000494:pharmacology; D008099:Liver / Q000166:cytology / Q000502:physiology*; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D011919:Rats, Inbred Strains; D011994:Recombinant Proteins / Q000494:pharmacology; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D014425:Turpentine / Q000494:pharmacology
C493495:CFH protein, human; D003176:Complement C3; D003180:Complement C3b Inactivator Proteins; D007375:Interleukin-1; D015850:Interleukin-6; D012333:RNA, Messenger; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D017242:Complement Factor H; D014425:Turpentine