Activin/follistatin in mouse lymphocytes

我们已经证明激活素是小鼠腹膜巨噬细胞产生基质金属蛋白酶-2的自分泌调节因子。逆转录-聚合酶链式反应检测到巨噬细胞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(激活素A)及其结合蛋白卵泡抑素，而不产生抑制素。脂多糖是一种有效的炎性刺激物质，可刺激巨噬细胞产生激活素βA亚单位和激活素活性。干扰素-γ不影响脂多糖刺激的巨噬细胞激活素的产生。I型和II型激活素受体在小鼠腹膜巨噬细胞中的表达表明，巨噬细胞产生的激活素是巨噬细胞功能的自分泌调节因子。明胶酶谱分析显示激活素可促进巨噬细胞产生基质金属蛋白酶-2。外源性加入卵泡抑素抑制…细胞基质金属蛋白酶-2活性更多的巨噬细胞，表明基质金属蛋白酶-2至少部分是由内源性激活素以自分泌方式调节的。竞争性RT-PCR结果显示，激活素和卵泡抑素在信使核糖核酸水平上调节了基质金属蛋白酶-2的活性。激活素和卵泡抑素均不影响巨噬细胞产生信使核糖核酸或基质金属蛋白酶-9的活性。由于基质金属蛋白酶-2是控制基底膜胶原降解的关键和限速酶，激活素可能在炎症状态下巨噬细胞通过基底膜的迁移和渗透中发挥作用。激活素在许多生物系统中是一种强大的细胞生长和分化因子。然而，到目前为止，激活素在免疫系统中的表达和功能尚不清楚。在这里，我们展示了活化素βA、结合蛋白(卵泡抑素)及其受体在B淋巴细胞中的表达。此外，我们还显示了激活素、卵泡抑素和激活素受体在B淋巴细胞激活后表达的动态变化，以发挥激活素的作用。培养的B淋巴细胞中激活素β基因表达水平升高，而卵泡抑素基因表达水平降低。B淋巴细胞培养上清液中的净激活素活性也随着mRNA水平的变化而增加。此外，卵清蛋白免疫小鼠后，B淋巴细胞激活素βA基因表达增加，卵泡抑素基因表达降低，提示无论在体内还是体外，B淋巴细胞激活素活性均受到调节。内毒素刺激和免疫后，除ActRI外，4种激活素受体和3种激活素受体的mRNAs表达分别降低。我们的发现表明，B淋巴细胞产生激活素，并作为激活素的靶标，这可能是激活素作为B淋巴细胞自分泌调节的可能作用。较少

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