Fibronectin modulates interleukin 6 and fibronectin synthesis of human glomerular mesangial cells in culture.
In this paper we report that fibronectin (FN) and its proteolytic 120-kD fragment regulate synthesis and secretion of interleukin 6 (IL-6) and of FN by human glomerular mesangial cells. While intact FN and a fragment derived from the heparin-binding domain had no effect on IL-6 secretion, the 120-kD FN fragment containing the cell attachment site stimulated secretion by 40-fold. The same FN fragment reduced FN secretion and the steady state mRNA level by 80%. The intact FN showed only a weak inhibitory effect (+/- 30%); the 30-kD fragment containing the heparin-binding domain had no effect. The effects of the 120-kD FN were inhibited by the peptide RGDS, implying participation of the cell attachment site in signal transduction. An antibody to the alpha-chain of VLA-3 mimicked the effect of the 120-kD FN, whereas an antibody to the alpha-chain of VLA-5 was partly inhibitory. Taken together, the data suggest that FN by interacting with its receptors differentially regulates the protein synthesis of glomerular mesangial cells, promoting IL-6 secretion and inhibiting FN synthesis.
Schieren
G
G
Institut für Immunologie der Universität Heidelberg, Deutschland.
Bürger
A
A
Braunger
M
M
Filsinger
S
S
Hänsch
G M
GM
D000906:Antibodies / Q000494:pharmacology; D002478:Cells, Cultured; D005353:Fibronectins / Q000096:biosynthesis* / Q000235:genetics / Q000494:pharmacology*; D005920:Glomerular Mesangium / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D039201:Integrin alpha3beta1; D016023:Integrins / Q000037:antagonists & inhibitors / Q000502:physiology; D015850:Interleukin-6 / Q000096:biosynthesis*; D009842:Oligopeptides / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D017469:Receptors, Fibronectin / Q000037:antagonists & inhibitors / Q000502:physiology
D000906:Antibodies; D005353:Fibronectins; D039201:Integrin alpha3beta1; D016023:Integrins; D015850:Interleukin-6; D009842:Oligopeptides; D010446:Peptide Fragments; D012333:RNA, Messenger; D017469:Receptors, Fibronectin; C046617:arginyl-glycyl-aspartyl-serine