Synergistic effects of retinoic acid and IL-1beta on expression of the bone-type alkaline phsphatase and retinoid receptors in small intestinal epithelial cells.

视黄酸和IL-1β对小肠上皮细胞中骨型碱性磷酸酶和类视黄醇受体表达的协同作用。

• 批准号: 08670599
• 负责人: NIKAWA Takeshi
• 金额: $ 1.34万
• 依托单位: THE UNIVERSITY OF TOKUSHIMA
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1996
• 资助国家: 日本
• 起止时间: 1996 至 1997
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08670599/
• 关键词: Retinoic acid; Interleukin-1beta; IEC-6 cells; retinoic acid receptor; liver; bone; kidney alkaline phosphatase; Caco-2 cells; インターロイキン-1; レチノイドXレセプター; レチノイドXレセプター応答領域

Last year, we reported that simultaneous addition of retinoic acid (RA) and IL-1beta induced a number of proteins as well as liver/bone/kidney alkaline phosphatase (L/B/K ALP) in rat intestinal epithelial IEC-6 cell line. In the subsequent studies, we found that the L/B/K ALP up-regulated with RA and IL-1beta had the bone-type leader sequence, but not liver-type one. Gel mobility shift assay for the putative RXRE showed that the binding activity was synergistically stimulated by the simultaneous treatment with RA and IL-1beta. We further studied the involvement of retinoid receptors and IL-1 receptor in these synergistic effects. The distinct of retinoic acid receptors (RARs) and retinoid X receptors (RXRs) were observed in IEC-6 cells after simultaneous treatment with RA and IL-1beta. RARs alpha and beta, and RXRs alpha and beta were synergistically expressed by RA and IL-1beta, while the expression of RARgamma and RXRgamma were not changed by the simultaneous treatment. The enhancement of RARbeta mRNA expression was the most remarkable among these receptors. It was of interest that IL-1beta increased the mRNA level of RARbeta, but RA itself did not. In contrast, the mRNA level of IL-1 receptor type-I were not changed even after the simultaneous treatment. These finding suggested that up-regulation of retinoid receptors, especially RARbeta, may participated in the synergistic effects of RA and IL-1beta. In a separate experiment, it was also found that simultaneous treatment with RA and IL-1beta synergisticaly increased cathepsin activities in human adenocarcinoma Caco-2 cells. Thus, we will provide the evidence suggesting that IL-1beta may regulate the protein synthesis in intestinal epithelial cells.

去年，我们报道说，在大鼠肠上皮IEC-6细胞系中，同时添加视黄酸（RA）和IL-1BETA诱导了许多蛋白质以及肝脏/骨/肾脏/肾脏碱性磷酸酶（L/B/K ALP）。在随后的研究中，我们发现用RA和IL-1Beta上调的L/B/K ALP具有骨型领位序列，但没有肝型。推定的RXRE的凝胶迁移率分析表明，与RA和IL-1Beta同时处理的结合活性是协同刺激的。我们进一步研究了类维生素性受体和IL-1受体在这些协同作用中的参与。与RA和IL-1BETA同时处理后，在IEC-6细胞中观察到视黄酸受体（RARS）和类视黄素X受体（RXR）的不同。 RARS Alpha和Beta，RXRS Alpha和Beta通过RA和IL-1Beta协同表达，而Rargamma和Rxrgamma的表达并未通过同时治疗而改变。在这些受体中，rarbeta mRNA表达的增强是最引人注目的。 IL-1Beta提高了Rarbeta的mRNA水平，但RA本身并没有提高。相反，即使在同时治疗后，IL-1受体I型的mRNA水平也不会改变。这些发现表明，类维生素性受体，尤其是Rarbeta的上调可能参与RA和IL-1Beta的协同作用。在另外一个实验中，还发现与RA和IL-1BETA协同作用同时治疗可增加人CACO-2细胞中的组织蛋白酶活性。因此，我们将提供证据表明IL-1BETA可以调节肠上皮细胞中的蛋白质合成。

项目成果

K.Rokutan, T.Nikawa et al.: "Implications of heat shock/stress proteins for medicine and disease." J.Med.Invest.44. (1998)

K.Rokutan、T.Nikawa 等人：“热休克/应激蛋白对医学和疾病的影响。”

K.Rokutan, T.Nikawa et al.: "Oxidant-induced activation of nuclear factor-kappa B in cultured guinea pig gastric epithelial cells." Dig.Dis.Sci.42. 1880-1889 (1997)

K.Rokutan、T.Nikawa 等人：“培养的豚鼠胃上皮细胞中氧化剂诱导的核因子-κ B 激活。”

二川 健、六反 一仁: "医学のあゆみ:小腸上皮細胞の分化と分子生物学" 医歯薬出版, (1996)

Ken Futakawa、Kazuhito Rokutan：“医学史：小肠上皮细胞的分化和分子生物学”石药出版社，（1996）

K.Rokutan, T.Nikawa et al.: "Implications of heat shock/stress prteins for medicine and disease." J.Med.Invest.44. (1998)

K.Rokutan、T.Nikawa 等人：“热休克/应激蛋白对医学和疾病的影响。”

S.Teshima, K.Rokutan, T.Nikawa, Y.Kido and K.Kishi: "Alteration of the respiratory burst and phagocytosis of macrophages under protein malnutrition." J.Nutr.Sci.Vitaminol.41. 127-137 (1995)

S.Teshima、K.Rokutan、T.Nikawa、Y.Kido 和 K.Kishi：“蛋白质营养不良下呼吸爆发和巨噬细胞吞噬作用的改变。”