Chesnokova V, Melmed S
Cedars-Sinai Research Institute- UCLA School of Medicine, Los Angeles, California 90048, USA.
Endocrinology. 2000 Nov;141(11):4032-40. doi: 10.1210/endo.141.11.7778.
The pleiotropic cytokine leukemia inhibitory factor (LIF) is expressed in murine hypothalamus and pituitary and increases POMC gene transcription and ACTH secretion in vitro and in vivo. As hypothalamic pituitary adrenal (HPA) axis activation during inflammation is an important protective mechanism, we determined whether LIF stimulates the HPA inflammatory stress response. Two experimental models were employed: s.c. injection of complete Freund's adjuvant (CFA) and i.m. administration of turpentine. Hypothalamic LIF gene expression was increased up to 5 days after CFA, and up to 24 h after turpentine. LIF induction was concordant with elevated plasma ACTH and corticosterone levels and pituitary POMC messenger RNA (mRNA) expression. Pituitary levels of LIF-inducible signaling inhibitor (SOCS 3) mRNA were stimulated 3-fold after CFA and turpentine treatment. In contrast, in LIF knockout mice (LIFKO) pituitary POMC mRNA levels and plasma ACTH and corticosterone responses to both inflammatory challenges were markedly lower than in wild-type (WT) animals. Injection of exogenous LIF (5 microg) to turpentine-treated LIFKO mice induces POMC gene expression. These results indicate that LIF is an essential component for the neuroendocrine response to inflammatory processes.
多效性细胞因子白血病抑制因子（LIF）在小鼠下丘脑和垂体中表达，并在体外和体内增加阿黑皮素原（POMC）基因转录和促肾上腺皮质激素（ACTH）分泌。由于炎症期间下丘脑-垂体-肾上腺（HPA）轴激活是一种重要的保护机制，我们确定LIF是否刺激HPA炎症应激反应。采用了两种实验模型：皮下注射完全弗氏佐剂（CFA）和肌肉注射松节油。CFA注射后长达5天以及松节油注射后长达24小时，下丘脑LIF基因表达增加。LIF的诱导与血浆ACTH和皮质酮水平升高以及垂体POMC信使核糖核酸（mRNA）表达一致。CFA和松节油处理后，垂体中LIF诱导的信号抑制剂（SOCS 3）mRNA水平增加了3倍。相比之下，在LIF基因敲除小鼠（LIFKO）中，垂体POMC mRNA水平以及血浆ACTH和皮质酮对两种炎症刺激的反应明显低于野生型（WT）动物。向经松节油处理的LIFKO小鼠注射外源性LIF（5微克）可诱导POMC基因表达。这些结果表明，LIF是神经内分泌对炎症过程反应的重要组成部分。
