Role of dexamethasone and oncostatin M on the formation of vacuoles in human fetal liver cells.
Combined treatment with dexamethasone and oncostatin M (DEX/OSM) or interleukin-6 (DEX/IL-6) resulted in the appearance of numerous large vacuoles in human fetal liver (HFL) cells and showed synergistic effects on the formation of vacuoles. The number of vacuoles formed by DEX, DEX/OSM, or DEX/IL-6 was significantly suppressed by RU-486, a glucocorticoid receptor antagonist. On the other hand, the size of vacuoles formed by OSM, IL-6, DEX/OSM, or DEX/IL-6 was significantly decreased to about 65% by madindoline A (MDL-A), which is a non-peptide antagonist of gp130 and an inhibitor of cytokines, such as IL-6, mediated by gp130 homodimerization, while RU-486 did not affect the size of vacuoles. Expression of IL-6 mRNA in HFL cells was markedly induced by OSM. Expression of IL-6R mRNA was induced by DEX. These results indicate that DEX contributes to the formation of vacuoles through glucocorticoid receptors and that OSM and IL-6 contribute to enlargement of these vacuoles.
Teramoto
Tsuyoshi
T
Department of Pharmacy, Shinshu University Hospital, Matsumoto, Japan.
Matsunaga
Tamihide
T
Toba
Mie
M
Sunazuka
Toshiaki
T
Omura
Satoshi
S
Ohmori
Shigeru
S
D000893:Anti-Inflammatory Agents / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology; D002478:Cells, Cultured; D050822:Cytokine Receptor gp130 / Q000096:biosynthesis / Q000235:genetics; D003907:Dexamethasone / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D005333:Fetus / Q000378:metabolism; D006131:Growth Inhibitors / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D006727:Hormone Antagonists / Q000494:pharmacology; D006801:Humans; D007211:Indoles / Q000494:pharmacology; D015850:Interleukin-6 / Q000096:biosynthesis; D008099:Liver / Q000166:cytology* / Q000196:embryology / Q000648:ultrastructure; D015735:Mifepristone / Q000494:pharmacology; D053683:Oncostatin M / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D019947:Receptors, Interleukin-6 / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014617:Vacuoles / Q000502:physiology*
D000893:Anti-Inflammatory Agents; D019086:Bridged Bicyclo Compounds, Heterocyclic; D006131:Growth Inhibitors; D006727:Hormone Antagonists; D007211:Indoles; D015850:Interleukin-6; D012333:RNA, Messenger; D019947:Receptors, Interleukin-6; C103158:madindoline A; D053683:Oncostatin M; D050822:Cytokine Receptor gp130; D015735:Mifepristone; D003907:Dexamethasone