Metallothionein induction by restraint stress: role of glucocorticoids and IL-6.
Restraint stress increased liver metallothionein-I (MT-I) mRNA and MT-I+II protein levels. The glucocorticoid receptor antagonist RU 486 decreased this response. In contrast, adrenalectomy only decreased MT-I+II protein levels. Moreover, corticosterone or progesterone did not reverse the effect of RU 486. These results suggest that glucocorticoids are important for MT-I+II protein synthesis but not for MT-I mRNA accumulation during restraint stress, and that other factors must be involved in this process. Interleukin-6 (IL-6) deficient mice showed a significant decrease of restraint stress-induced liver MT-I mRNA levels (approximately 30% of IL-6+/+ mice) up to approximately 4-5 hours after the onset of stress. Western blotting of hepatic nuclear proteins showed that the IL-6 responsive transcription factor Stat3, which has been shown to mediate MT induction by inflammation, was also activated by restraint stress. Results after extended periods of restraint stress indicate that IL-6 participates early and transiently in the process. The analysis of the expression of the acute phase plasma protein serum amyloid A suggests that restraint stress elicits an acute phase response similar to that caused by inflammation.
Hernández
J
J
Departamento de Biología Celular, de Fisiología y de Inmunología, Unidad de Fisiologia Animal, Facultad de Ciencias, Universidad Autónoma de Barcelona, Barcelona, Bellaterra, 08193, Spain.
Carrasco
J
J
Belloso
E
E
Giralt
M
M
Bluethmann
H
H
Kee Lee
D
D
Andrews
G K
GK
Hidalgo
J
J
D000315:Adrenalectomy; D000818:Animals; D003345:Corticosterone / Q000494:pharmacology; D004268:DNA-Binding Proteins / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D005938:Glucocorticoids / Q000502:physiology*; D015850:Interleukin-6 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D007700:Kinetics; D008668:Metallothionein / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D015735:Mifepristone / Q000494:pharmacology; D011374:Progesterone / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics; D012149:Restraint, Physical; D050796:STAT3 Transcription Factor; D013315:Stress, Psychological / Q000276:immunology / Q000503:physiopathology*; D013997:Time Factors; D015534:Trans-Activators / Q000378:metabolism; D014158:Transcription, Genetic
D004268:DNA-Binding Proteins; D005938:Glucocorticoids; D015850:Interleukin-6; D012333:RNA, Messenger; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse; D015534:Trans-Activators; D015735:Mifepristone; D011374:Progesterone; D008668:Metallothionein; D003345:Corticosterone