Chimeric molecule IL-6/soluble IL-6 receptor is a potent mitogen for fetal hepatocytes.
A novel recombinant molecule, termed IL-6c and consisting of a chimera of interleukin 6 (IL-6) and its soluble receptor is extremely potent in stimulating proliferation of hematopoietic progenitors. We investigated the effect of the IL-6c on the proliferation and differentiation of E14 fetal hepatocytes. IL-6c, in a dose-dependent manner, stimulated proliferation of E14 fetal rat hepatocytes. Adult hepatocyte mitogens together with IL-6c showed no further effect on proliferation. Hematopoietic stem cells mitogens SCF and flt3 ligand (FL) were also mitogenic for fetal hepatocytes, but did not further enhance the effect of IL-6c on cell proliferation. IL-6c decreased expression of fetal markers alpha-fetoprotein (AFP) and gamma-glutamyltranspeptidase, and induced expression of adult enzyme glucose-6-phosphatase (Gluc-6-P) in E14 hepatocytes. On the other hand, IL-6c strongly reduced, in a dose-dependant manner, expression of albumin and tyrosine aminotransferase (TAT). However, when the cells were grown for 3 days with IL-6c, and IL-6c was removed for the next 5 days, expression of albumin and TAT returned to levels found in control cultures. In conclusion, IL-6c stimulated proliferation and affected gene expression in fetal hepatocytes in culture.
Zvibel
Isabel
I
Liver Unit, Gastroenterology Institute, Tel Aviv Sourasky Medical Center, Weizman 6, Tel Aviv, Israel. isab@tasmc.health.gov.il
Brill
Shlomo
S
Kariv
Revital
R
Traister
Alexandra
A
Golan
Talia
T
Chebath
Judith
J
Halpern
Zamir
Z
Revel
Michel
M
Oren
Ran
R
D000251:Adenosine Triphosphatases / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D002455:Cell Division / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D018819:Dipeptidyl Peptidase 4 / Q000378:metabolism; D005312:Fetal Blood / Q000166:cytology; D005333:Fetus / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D005434:Flow Cytometry; D005952:Glucose-6-Phosphatase / Q000378:metabolism; D006003:Glycogen / Q000096:biosynthesis; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D022781:Hepatocytes / Q000166:cytology / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D007150:Immunohistochemistry; D008934:Mitogens / Q000494:pharmacology*; D051381:Rats; D011916:Rats, Inbred F344; D019947:Receptors, Interleukin-6 / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D012995:Solubility; D005723:gamma-Glutamyltransferase / Q000378:metabolism
D008934:Mitogens; D019947:Receptors, Interleukin-6; D011994:Recombinant Proteins; D006003:Glycogen; D005723:gamma-Glutamyltransferase; D005952:Glucose-6-Phosphatase; D018819:Dipeptidyl Peptidase 4; D000251:Adenosine Triphosphatases