title: Role of macrophage migration inhibitory factor in glucocorticoid release and glucocorticoid receptor function in rats.
abstract: Experimental evidence indicates that macrophage migration inhibitory factor (MIF) plays a pathological role in the development of glucocorticoid resistance in sepsis patients. However, the impact of MIF on glucocorticoid release and the functions of the glucocorticoid receptor (GR) have not been studied extensively. In this study, exogenous administration of recombinant mouse macrophage migration inhibitory factor (rMIF), at a dose close to the levels found in the blood of sepsis patients, significantly enhanced serum corticosterone concentration but neither altered circulatory function nor stimulated nitric oxide (NO) release in rats. Incubation of cultured rat cardiomyocytes with 10 ng/ml and 20 ng/ml of rMIF did not cause changes in GR protein expression compared to control values but significantly decreased the expression of heat shock protein 90. GR specific binding activity was significantly inhibited by incubation of rat hepatocytes with 20 ng/ml rMIF alone or with 100 μmol/L L-NAME (a NO synthase inhibitor), and no significant difference was found between the two groups. These results suggest that elevated MIF levels in sepsis patients, at least in part, play an important role in the development of glucocorticoid resistance and that the NO signaling pathway is not involved in this pathological process.
authors.affiliation: Department of Anesthesiology, Zhongda Hospital and School of Medicine, Southeast University, Nanjing, China. jinglg@gmail.com
authors.forename: Liang
authors.initials: L
authors.lastname: Jing
authors.forename: Min
authors.initials: M
authors.lastname: Bu
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001794:Blood Pressure / Q000187:drug effects; D003345:Corticosterone / Q000097:blood; D005938:Glucocorticoids / Q000378:metabolism*; D018841:HSP90 Heat-Shock Proteins / Q000378:metabolism; D006339:Heart Rate / Q000187:drug effects; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D008263:Macrophage Migration-Inhibitory Factors / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D051379:Mice; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009566:Nitrates / Q000378:metabolism; D009573:Nitrites / Q000378:metabolism; D011485:Protein Binding / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D011965:Receptors, Glucocorticoid / Q000378:metabolism*; D011994:Recombinant Proteins / Q000494:pharmacology
chemical_list: D005938:Glucocorticoids; D018841:HSP90 Heat-Shock Proteins; D008263:Macrophage Migration-Inhibitory Factors; D009566:Nitrates; D009573:Nitrites; D011965:Receptors, Glucocorticoid; D011994:Recombinant Proteins; D019331:NG-Nitroarginine Methyl Ester; D003345:Corticosterone