Macrophage Migration Inhibitory Factor Is Released from Pituitary Folliculo-Stellate-Like Cells by Endotoxin and Dexamethasone and Attenuates the Steroid-Induced Inhibition of Interleukin 6 Release

Macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine produced by peripheral immune cells and also by endocrine cells in the anterior pituitary gland. MIF exerts its proinflammatory actions in the host-defense system by blocking the inhibitory effects of glucocorticoids on the r...

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Bibliographic Details
Published in:Endocrinology (Philadelphia) 2005-01, Vol.146 (1), p.35-43
Main Authors: Tierney, Tanya, Patel, Reshma, Stead, Caroline A. S, Leng, Lin, Bucala, Richard, Buckingham, Julia C
Format: Article
Language:English
Subjects:
Animals
Biological and medical sciences
Cell Line
Corticotropin-Releasing Hormone - administration & dosage
Corticotropin-Releasing Hormone - pharmacology
Dexamethasone - administration & dosage
Dexamethasone - pharmacology
Dose-Response Relationship, Drug
Endotoxins - administration & dosage
Endotoxins - pharmacology
Fundamental and applied biological sciences. Psychology
Glucocorticoids - administration & dosage
Glucocorticoids - pharmacology
Immunohistochemistry
Interleukin-6 - antagonists & inhibitors
Interleukin-6 - metabolism
Macrophage Migration-Inhibitory Factors - administration & dosage
Macrophage Migration-Inhibitory Factors - metabolism
Macrophage Migration-Inhibitory Factors - pharmacology
Male
Pituitary Gland - cytology
Pituitary Gland - metabolism
Rats
Rats, Sprague-Dawley
Recombinant Proteins - pharmacology
Tissue Distribution
Vertebrates: endocrinology
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Summary:Macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine produced by peripheral immune cells and also by endocrine cells in the anterior pituitary gland. MIF exerts its proinflammatory actions in the host-defense system by blocking the inhibitory effects of glucocorticoids on the release of other proinflammatory cytokines (e.g. IL-1, IL-6, TNFα). Reports that pituitary folliculo-stellate (FS) cells share many characteristics with immune cells led us to propose that these cells may serve as an additional source of MIF in the pituitary and that pituitary-derived MIF may act in an autocrine or paracrine manner to modulate endotoxin-induced cytokine release from FS cells. In the present study we addressed this hypothesis by using 1) immunohistochemistry to localize MIF in primary pituitary tissue and 2) well-characterized FS (TtT/GF), corticotroph (AtT20), and macrophage/monocyte (RAW 264.7) cell lines to explore the effects of CRH, endotoxin, and dexamethasone on MIF release and to examine the effects of MIF on IL-6 release. Our immunohistochemical study showed that MIF is expressed in abundance in S100-positive FS cells and also in other pituitary cell types. All three cell lines expressed MIF protein and responded to endotoxin (10–1000 ng/ml, 24 h) and dexamethasone (100 pm to 10 nm, 24 h) with concentration-dependent increases in MIF release. CRH (10–100 nm) also stimulated MIF release from AtT20 cells but, unlike endotoxin and dexamethasone, it had no effect on MIF release from TtT/GF or RAW cells. Recombinant MIF did not affect the basal release of IL-6 from TtT/GF cells; however, it effectively reversed the inhibitory effects of dexamethasone (1 nm) on the endotoxin-induced release of IL-6 from these cells. The results suggest that the FS cells are both a source of and a target for MIF and raise the possibility that MIF serves as a paracrine/autocrine factor in the pituitary gland that contributes to the protective neuroendocrine response to endotoxin.
ISSN:0013-7227
1945-7170
DOI:10.1210/en.2004-0946