Activin/follistatin in mouse lymphocytes

小鼠淋巴细胞中的激活素/卵泡抑素

• 批准号: 10660295
• 负责人: OGAWA Kenji
• 金额: $ 2.62万
• 依托单位: RIKEN
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1998
• 资助国家: 日本
• 起止时间: 1998 至 1999
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10660295/
• 关键词: mouse; lymphocytes; macrophages; activin; follistatin; Tリンパ球; CD3; MMP

We have demonstrated that activin is an autocrine regulator of matrix metalloproteinase (MMP) -2 production in mouse peritoneal macrophages. Although the expression of βA subunit and follistatin was detected, that of α and βB subunit was not found in macrophages by reverse transcription-polymerase chain reaction (RT-PCR), suggesting that macrophages produce activin (activin A) and its binding protein, follistatin, but not inhibin. LPS, a potent inflammatory stimulus, stimulated the production of activin βA subunit mRNA and activin activity from mactophages. LPS-stimulated activin production from macrophages was not affected by IFN-γ. The expression of both type I and type II activin receptors in mouse peritoneal macrophages suggests that activin produced by macrophages acts as an autocrine regulator of macrophage function. Gelatin zymography analysis revealed that the production of MMP-2 from macrophages was enhanced by activin. Exogenously added follistatin suppressed MMP-2 activity f … More rom macrophages, indicating that MMP-2 is regulated, at laeast in part, by endogenous activin in an autocrine manner. MMP-2 activity was regulated by activin and follistatin at a mRNA level as revealed by competitive RT-PCR. Neither activin nor follistatin affected the production of mRNA or the activity of MMP-9 from macrophages. Since MMP-2 constitutes the key and rate-limiting proteinase governing the degradation of basement membrane collagens, activin may have a role in migration and infiltration of macrophages through the basement membrane in an inflammatory state.Activin is a potent cell growth and differentiation factor in many biological systems. However, expression and function of activin in the immune system are so far unknown. Here we demonstrated mRNA expression of activin βA, the binding protein (follistatin), and the receptors in B lymphocytes. In addition, we also show the dynamic changes in mRNA expression of activin, follistatin and activin receptors in response to activation of B lymphocytes to exert activin's action. Activin βA mRNA level was increased in the cultured B lymphocytes by LPS, whereas follistatin mRNA was decreased. Consistent with changes in mRNA level, net activin activity in the culture supernatant of B lymphocytes was also increased by LPS. Furthermore, immunization of mice with ovalbumin resulted in the increased activin βA mRNA and decreased follistatin mRNA in B lymphocytes, suggesting regulation of activin activity in B lymphocytes not only in vitro but also in vivo. The LPS stimulation and the immunization resulted in decreases in mRNAs expression of all four and three activin receptors except for ActRI, respectively. Our findings indicate that B lymphocytes produce activin and are target for activin, which might be the possible role of activin as an autocrine regulator of B lymphocytes. Less

我们已经证明激活素是小鼠腹腔巨噬细胞中基质金属蛋白酶（MMP）-2产生的自分泌调节剂。逆转录-聚合酶链反应（RT-PCR）检测到βA亚基和卵泡抑素的表达，但未检测到α和βB亚基的表达，提示巨噬细胞产生激活素（activin A）及其结合蛋白卵泡抑素，而不产生卵泡抑素。LPS是一种强有力的炎症刺激物，刺激巨噬细胞产生激活素βA亚基mRNA和激活素活性。LPS刺激的巨噬细胞激活素的产生不受IFN-γ的影响。小鼠腹腔巨噬细胞中I型和II型激活素受体的表达表明巨噬细胞产生的激活素作为巨噬细胞功能的自分泌调节剂。明胶酶谱分析表明，MMP-2的生产从巨噬细胞激活素增强。外源性卵泡抑素抑制MMP-2活性， ...更多信息 从巨噬细胞，表明MMP-2的调节，至少部分，由内源性激活素自分泌的方式。竞争性RT-PCR结果显示激活素和卵泡抑素在mRNA水平调控MMP-2活性。激活素和卵泡抑素均不影响巨噬细胞MMP-9的mRNA表达和活性。由于MMP-2是控制基底膜胶原降解的关键和限速蛋白酶，激活素可能在炎症状态下巨噬细胞穿过基底膜的迁移和浸润中起作用。然而，迄今为止，激活素在免疫系统中的表达和功能尚不清楚。在此，我们证明了激活素βA、结合蛋白（卵泡抑素）和受体在B淋巴细胞中的mRNA表达。此外，我们还显示激活素，卵泡抑素和激活素受体的mRNA表达的动态变化响应于激活的B淋巴细胞发挥激活素的作用。LPS可使培养的B淋巴细胞激活素βA mRNA表达增加，而卵泡抑素mRNA表达降低。与mRNA水平的变化一致，LPS也增加了B淋巴细胞培养上清液中的净激活素活性。卵清蛋白免疫小鼠后，B淋巴细胞中激活素βA mRNA表达增加，卵泡抑素mRNA表达减少，提示激活素对B淋巴细胞活性的调节不仅在体外，而且在体内也存在。LPS刺激和免疫分别导致除ActRI外的所有四种和三种激活素受体的mRNA表达降低。我们的研究结果表明，B淋巴细胞产生激活素，并为激活素的目标，这可能是激活素作为B淋巴细胞的自分泌调节剂的可能作用。少