Regulation of fibronectin synthesis by interleukin-1 and interleukin-6 in rat hepatocytes.
The authors have observed previously that recombinant human interleukin-1 (rhIL-1) administered into rats increased plasma fibronectin (Fn) level concomitant with the increase of Fn in the liver. Because IL-1 induces interleukin-6 (IL-6) in certain cell types, the IL-1 effect might be mediated by IL-6. To evaluate this possibility, the effect of recombinant human interleukin-6 (rhIL-6), rhIL-1 alpha, and rhIL-1 beta on Fn synthesis in cultured rat hepatocytes was studied. It was shown that rhIL-6 increased Fn synthesis in hepatocytes, in contrast, rhIL-1 alpha, rhIL-I beta and TNF did not have any effect on Fn synthesis. When we studied the interaction of IL-1 and IL-6, IL-1 did not exhibit any synergistic effect with IL-6. Conditioned medium (CM) from rhIL-1 stimulated peripheral blood monocytes (PBM) increased the Fn synthesis, and its activity was neutralized significantly by anti-rhIL-6 antibodies. The CM from rhIL-1-stimulated PBM was analyzed by enzyme linked immunosorbent assay and revealed the increase of IL-6. Furthermore, it was found that intraperitoneal administration of rhIL-1 induced IL-6 into blood. The administration of rhIL-6 into rats increased circulating Fn levels. These results strongly suggest that the in vivo effect of IL-1 on Fn synthesis is mediated by IL-6.
Institute of Clinical Medicine, University of Tsukuba, Ibaraki, Japan.
T
T
Hagiwara
H
H
Suzuki
I
I
Kono
H
H
Kashiwagi
Y
Y
Akiyama
K
K
Onozaki
D000818:Animals; D001685:Biological Factors / Q000494:pharmacology; D002478:Cells, Cultured; D002648:Child; D003470:Culture Media / Q000494:pharmacology; D016207:Cytokines; D005353:Fibronectins / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007375:Interleukin-1 / Q000378:metabolism / Q000494:pharmacology*; D015850:Interleukin-6 / Q000378:metabolism / Q000494:pharmacology*; D008099:Liver / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D008297:Male; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011994:Recombinant Proteins / Q000494:pharmacology
D001685:Biological Factors; D003470:Culture Media; D016207:Cytokines; D005353:Fibronectins; D007375:Interleukin-1; D015850:Interleukin-6; D012333:RNA, Messenger; D011994:Recombinant Proteins