松果體屬于室周器官,，對(duì)機(jī)體的防御反應(yīng)起著關(guān)鍵作用,，松果體損傷會(huì)引起褪黑激素被抑制。褪黑激素(Melatonin)主要是由哺乳動(dòng)物和人類的松果體產(chǎn)生的一種胺類激素,。近年來,，國內(nèi)外對(duì)褪黑激素的生物學(xué)功能，尤其是作為膳食補(bǔ)充劑的保健功能進(jìn)行了廣泛的研究,，表明其具有促進(jìn)睡眠,、調(diào)節(jié)時(shí)差、抗衰老,、調(diào)節(jié)免疫,、抗腫瘤等多項(xiàng)生理功能。
先前已有研究表明體外培養(yǎng)的松果體表達(dá)Toll樣受體4（TLR4）和腫瘤壞死因子受體1（TNFR1）,，當(dāng)接受脂多糖（LPS）的刺激時(shí)能產(chǎn)生腫瘤壞死因子,。近日PLoS ONE雜志上的一項(xiàng)研究目評(píng)估了是否是存在于松果體中的星形膠質(zhì)細(xì)胞、小膠質(zhì)細(xì)胞或松果體細(xì)胞產(chǎn)生腫瘤壞死因子,，以了解松果體活動(dòng),、褪黑激素的生產(chǎn)與免疫功能之間的相互作用。
實(shí)驗(yàn)中用LPS刺激體外培養(yǎng)的松果腺或松果體，腫瘤壞死因子含量的測(cè)定采用酶聯(lián)免疫吸附試驗(yàn),，TLR4和TNFR1的表達(dá)用共聚焦顯微鏡進(jìn)行分析,，免疫組化分析小膠質(zhì)細(xì)胞形態(tài)。
在本研究中,，數(shù)據(jù)表明盡管松果腺的主要細(xì)胞類型（松果體細(xì)胞,、星形膠質(zhì)細(xì)胞和小膠質(zhì)細(xì)胞）表達(dá)TLR4，但LPS誘導(dǎo)腫瘤壞死因子的生產(chǎn)由小膠質(zhì)細(xì)胞介導(dǎo),。這種效果是由于核因子kappa B（NF-KB）的活化帶來的,。
此外，研究人員還觀察到脂多糖激活小膠質(zhì)細(xì)胞和調(diào)節(jié)松果體TNFR1的表達(dá),。由于腫瘤壞死因子已經(jīng)證明與炎癥反應(yīng)的放大和延長有關(guān),，松果體小膠質(zhì)細(xì)胞產(chǎn)生腫瘤壞死因子表明膠質(zhì)松果腺細(xì)胞網(wǎng)絡(luò)能調(diào)節(jié)褪黑激素的釋放。這項(xiàng)研究有助從分子與細(xì)胞水平上了解在先天免疫反應(yīng)中褪黑激素是如何調(diào)節(jié)合成的,，研究結(jié)果再次證實(shí)松果體在免疫反應(yīng)中充當(dāng)傳感器的作用,。（生物谷：Bioon.com）
doi:10.1371/journal.pone.0040142
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Glia-Pinealocyte Network: The Paracrine Modulation of Melatonin Synthesis by Tumor Necrosis Factor (TNF)
Sanseray da Silveira Cruz-Machado, Luciana Pinato, Eduardo Koji Tamura, Cláudia Emanuele Carvalho-Sousa,
The pineal gland, a circumventricular organ, plays an integrative role in defense responses. The injury-induced suppression of the pineal gland hormone, melatonin, which is triggered by darkness, allows the mounting of innate immune responses. We have previously shown that cultured pineal glands, which express toll-like receptor 4 (TLR4) and tumor necrosis factor receptor 1 (TNFR1), produce TNF when challenged with lipopolysaccharide (LPS). Here our aim was to evaluate which cells present in the pineal gland, astrocytes, microglia or pinealocytes produced TNF, in order to understand the interaction between pineal activity, melatonin production and immune function. Cultured pineal glands or pinealocytes were stimulated with LPS. TNF content was measured using an enzyme-linked immunosorbent assay. TLR4 and TNFR1 expression were analyzed by confocal microscopy. Microglial morphology was analyzed by immunohistochemistry. In the present study, we show that although the main cell types of the pineal gland (pinealocytes, astrocytes and microglia) express TLR4, the production of TNF induced by LPS is mediated by microglia. This effect is due to activation of the nuclear factor kappa B (NF-kB) pathway. In addition, we observed that LPS activates microglia and modulates the expression of TNFR1 in pinealocytes. As TNF has been shown to amplify and prolong inflammatory responses, its production by pineal microglia suggests a glia-pinealocyte network that regulates melatonin output. The current study demonstrates the molecular and cellular basis for understanding how melatonin synthesis is regulated during an innate immune response, thus our results reinforce the role of the pineal gland as sensor of immune status.
