催乳素和免疫系统

Ferrag Fatima, Lebrun Jean-Jacques, Touraine Philippe, Nagano Makoto, Dardenne Mireille, Kelly Paul A.
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引用次数: 10

摘要

催乳素(PRL)在许多物种中参与广泛的生理作用,其免疫调节作用已被充分证实。PRL受体已经从不同的物种中克隆出来。在大鼠和小鼠中至少有两种受体同种异构体(短型和长型),它们仅在细胞质结构域不同,由单个基因的选择性剪接产生,尽管在人类中只有长型存在。利用逆转录聚合酶链反应(RT-PCR),我们在人类、小鼠和大鼠的所有淋巴组织中检测到编码两种形式PRL受体的转录本,但在小鼠和大鼠中,两种形式的比例因动物而异。对于编码PRL本身的转录本,总是在人淋巴细胞中发现清晰的信号,偶尔在大鼠胸腺中发现。我们还建立了定量PCR (Q-PCR)方法来测定大鼠在发情周期的两个阶段胸腺和脾脏中转录本的绝对数量。两种形式的表达水平大致相当。最后,我们利用Nb2大鼠淋巴瘤细胞系作为模型系统,确定了与PRLR相关的酪氨酸激酶JAK2,并研究了PRL对细胞有丝分裂的作用。我们还发现,在PRL的刺激下,二聚化过程是PRLR和JAK2磷酸化的先决步骤,是信号转导通路中最早的事件。
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Prolactin and the Immune System

Prolactin (PRL) Is involved In a wide range of physiological effects in several species and its immunoregulatory role has already been well documented. The PRL receptor has been cloned from various species. There are at least two receptor isoforms (short and long) in rats and mice, which differ only in their cytoplasmic domains, generated by alternative splicing of a single gene, although in human only the long form exists. Using the reverse transcriptase-polymerase chain reaction (RT-PCR), we detected transcripts encoding both forms of PRL receptor in all lymphoid tissues examined in human, mouse, and rat, but in mouse and rat the ratio between the two forms was variable from animal to animal. Concerning the transcript encoding the PRL itself, a clear signal was always found in human lymphocytes and occasionally in rat thymus. We also developed a quantitative PCR (Q-PCR) in order to measure the absolute number of transcripts in thymus and spleen from rats at two stages of estrous cycle. The level of expression of the two forms was about equal. Finally, we identified the tyrosine kinase JAK2, which is constitutively associated with the PRLR, using the Nb2 rat lymphoma cell line as a model system with which to study the action of PRL on cell mitogenesis. We also showed that, after stimulation by PRL, the dimerization process is a prerequisite step for the phosphorylatlon of the PRLR and JAK2, which represents the earliest event in the signal transduction pathway.

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