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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
被引:37
作者:
Tierney, T
Patel, R
Stead, CAS
Leng, L
Bucala, R
Buckingham, JC
机构:
[1] Univ London Imperial Coll Sci Technol & Med, Fac Med, Div Neurosci & Psychol Med, Dept Cellular & Mol Neurosci, London W12 0NN, England
[2] Yale Univ, Sch Med, Dept Internal Med & Pathol, New Haven, CT 06520 USA
关键词:
D O I:
10.1210/en.2004-0946
中图分类号:
R5 [内科学];
学科分类号:
1002 ;
100201 ;
摘要:
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, TNFalpha). 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.
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页码:35 / 43
页数:9
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