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PMID: 1835380 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Interleukin-1 and tumour necrosis factor induce hepatic haem oxygenase. Feedback regulation by glucocorticoids.

The Biochemical journal ·Vol. 279 ( Pt 3) ·1991-11-01 ·Pages 891-4

Cantoni L, Rossi C, Rizzardini M, Gadina M, Ghezzi P

Abstract

During the acute-phase response to bacterial endotoxins [lipopolysaccharide (LPS)] in mice, the hepatic activity of haem oxygenase (HO) is increased. We investigated the effects of the potential humoral mediators of inflammation, interleukin-1 (IL-1) and tumour necrosis factor (TNF), on hepatic HO activity. In mice, IL-1 or TNF (5 micrograms) caused an elevation of HO activity comparable with that after LPS exposure (20 micrograms). The induction of HO by both cytokines was more pronounced in adrenalectomized mice. In the intact mice induction of HO activity by cytokines was observed earlier than depression of 7-ethoxycoumarin O-de-ethylase, a cytochrome P-450-dependent enzyme activity. Pretreatment with dexamethasone of the intact mice (3 mg/kg) or of the adrenalectomized mice (0.4 mg/kg) prevented the induction of HO activity caused by LPS and IL-1 respectively. These results suggest that: (1) HO activity is increased during an IL-1- or TNF-mediated acute-phase response, so haem metabolism might be a potential target of inflammation, and (2) HO induction by IL-1 and TNF does not require glucocorticoids, which in fact act as antagonists of this cytokine-induced effect.

MeSH Terms
7-Alkoxycoumarin O-Dealkylase/metabolism Acute-Phase Reaction/metabolism Animals Dexamethasone/pharmacology Enzyme Induction Glucocorticoids/pharmacology Heme Oxygenase (Decyclizing)/biosynthesis Interleukin-1/metabolism,pharmacology Lipopolysaccharides/physiology Liver/drug effects,enzymology Male Mice Receptors, Immunologic/antagonists & inhibitors,metabolism Receptors, Interleukin-1 Tumor Necrosis Factor-alpha/pharmacology
Chemicals
Glucocorticoids Interleukin-1 Lipopolysaccharides Receptors, Immunologic Receptors, Interleukin-1 Tumor Necrosis Factor-alpha Dexamethasone 7-Alkoxycoumarin O-Dealkylase Heme Oxygenase (Decyclizing)
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Cantoni L
Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy.
Rossi C
Rizzardini M
Gadina M
Ghezzi P
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Article Info
Journal
The Biochemical journal
Abbr.
Biochem J
ISSN
0264-6021
DOI
10.1042/bj2790891
Published
1991-11-01
Pages
891-4
Language
English
Region
England
NLM ID
2984726R
PMCID
PMC1151529
Subset
IM
External Links
PubMed source DOI: 10.1042/bj2790891 PMC Full Text View journal details
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