Journal
CYTOKINE
Volume 12, Issue 6, Pages 791-796Publisher
W B SAUNDERS CO
DOI: 10.1006/cyto.1999.0629
Keywords
acute phase response; glucocorticoids; interlukin 6; metallothionein; stress
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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 (similar to 30% of IL-6+/+ mice) up to similar to 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. (C) 2000 Academic Press.
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