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In vitro DNA synthesis of mouse hepatocytes stimulated by tumor necrosis factor is inhibited by glucocorticoids and prostaglandin D 2 but enhanced by retinoic acid
Author(s) -
Satoh Motonobu,
Yamazaki Masatoshi
Publication year - 1993
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.1041570114
Subject(s) - dna synthesis , endocrinology , tumor necrosis factor alpha , hepatocyte , retinoic acid , medicine , epidermal growth factor , cytokine , liver regeneration , corticosterone , in vitro , chemistry , hormone , biology , cell culture , regeneration (biology) , receptor , microbiology and biotechnology , biochemistry , genetics
Abstract We have recently shown that TNF is produced in liver rapidly after partial hepatectomy and that TNF can stimulate DNA synthesis of hepatocyte primary culture with its inhibition by interleukin 6 and transforming growth factor‐β, indicating a pivotal role of TNF and TNF‐driven cytokine induction in liver regeneration. We here examined the effects of biological or inflammatory mediators of low molecular weight on the in vitro DNA synthesis of hepatocytes stimulated by TNF. Simultaneous addition of dexamethasone markedly suppressed the growth‐stimulating action of TNF, maximally at 10 −7 M and effectively at about 10 −8 M. However, the growth‐stimulating effect of EGF was not affected by dexamethasone at all. Physiological glucocorticoids, corticosterone, and hydrocortisone showed virtually the same effect, but other steroid hormones, β‐estradiol, or progesterone did not. Retinoic acid at 10 −7 M, however, enhanced TNF‐stimulated hepatocyte DNA synthesis and even more effectively the growth response to FGF. PGD 2 at 20 μM was markedly suppressive but PGE 2 was not. The addition of indomethacin enhanced the hepatocyte in vitro growth by TNF and EGF at 2–20 μM. These results indicate that the growth of hepatocytes stimulated by TNF is up and down‐regulated by inflammatory mediators and hormones as well as cytokines and suggest the biological significance of TNF and TNF‐driven inflammatory reactions in liver regeneration. © 1993 Wiley‐Liss, Inc.