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 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.
Tierney
Tanya
T
Department of Cellular and Molecular Neuroscience, Division of Neuroscience and Psychological Medicine, Imperial College London, London W12 0NN, United Kingdom.
Patel
Reshma
R
Stead
Caroline A S
CA
Leng
Lin
L
Bucala
Richard
R
Buckingham
Julia C
JC
D000818:Animals; D002460:Cell Line; D003346:Corticotropin-Releasing Hormone / Q000008:administration & dosage / Q000494:pharmacology; D003907:Dexamethasone / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004731:Endotoxins / Q000008:administration & dosage / Q000494:pharmacology*; D005938:Glucocorticoids / Q000008:administration & dosage / Q000494:pharmacology*; D007150:Immunohistochemistry; D015850:Interleukin-6 / Q000378:metabolism*; D008263:Macrophage Migration-Inhibitory Factors / Q000008:administration & dosage / Q000378:metabolism* / Q000494:pharmacology; D008297:Male; D010902:Pituitary Gland / Q000166:cytology / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000494:pharmacology; D014018:Tissue Distribution; D000093242:Interleukin-6 Inhibitors
D003346:Corticotropin-Releasing Hormone; D003907:Dexamethasone; D004731:Endotoxins; D005938:Glucocorticoids; D015850:Interleukin-6; D008263:Macrophage Migration-Inhibitory Factors; D011994:Recombinant Proteins; D000093242:Interleukin-6 Inhibitors