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 is released from pituitary folliculo-stellate-like cells by endotoxin and dexamethasone and attenuates the steroid-induced inhibition of interleukin 6 release.
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DOI：
10.1210/en.2004-0946
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发表时间：
2004-11
期刊：
影响因子：
4.8
通讯作者：
T. Tierney;Reshma Patel;Caroline A S Stead;L. Leng;R. Bucala;J. Buckingham
中科院分区：
文献类型：
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作者：
T. Tierney;Reshma Patel;Caroline A S Stead;L. Leng;R. Bucala;J. Buckingham
巨噬细胞迁移抑制因子（MIF）是一种由外周免疫细胞和垂体前叶内分泌细胞产生的促炎细胞因子。 MIF 通过阻断糖皮质激素对其他促炎细胞因子（例如 IL-1、IL-6、TNFα）释放的抑制作用，在宿主防御系统中发挥促炎作用。垂体滤泡星状 (FS) 细胞与免疫细胞具有许多共同特征的报道使我们提出，这些细胞可能作为垂体中 MIF 的额外来源，并且垂体来源的 MIF 可能以自分泌或旁分泌方式调节 FS 细胞内毒素诱导的细胞因子释放。在本研究中，我们通过使用 1) 免疫组织化学来定位原发性垂体组织中的 MIF，以及 2) 充分表征的 FS (TtT/GF)、促肾上腺皮质激素细胞 (AtT20) 和巨噬细胞/单核细胞 (RAW 264.7) 细胞系来探讨 CRH、内毒素和地塞米松对 MIF 释放的影响，并检查 MIF 对 MIF 释放的影响。 IL-6 释放。我们的免疫组织化学研究表明，MIF 在 S100 阳性 FS 细胞以及其他垂体细胞类型中大量表达。所有三种细胞系均表达 MIF 蛋白，并对内毒素（10-1000 ng/ml，24 小时）和地塞米松（100 pM 至 10 nM，24 小时）做出反应，MIF 释放呈浓度依赖性增加。 CRH (10-100 nM) 还刺激 AtT20 细胞释放 MIF，但与内毒素和地塞米松不同，它对 TtT/GF 或 RAW 细胞释放 MIF 没有影响。重组MIF不影响TtT/GF细胞IL-6的基础释放；然而，它有效地逆转了地塞米松 (1 nM) 对内毒素诱导的这些细胞释放 IL-6 的抑制作用。结果表明，FS 细胞既是 MIF 的来源，也是 MIF 的靶标，并提出了 MIF 作为垂体中的旁分泌/自分泌因子的可能性，有助于对内毒素的保护性神经内分泌反应。
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.