Choi Hyeongjwa, Ignacio Rosa Mistica C, Lee Eun-Sook, Roby Katherine F, Terranova Paul F, Son Deok-Soo
Department of Biochemistry and Cancer Biology, Meharry Medical College, Nashville, TN 37208, USA.
Department of Pharmaceutical Sciences, College of Pharmacy, Florida A&M University, Tallahassee, FL 32301, USA.
Immune Netw. 2017 Aug;17(4):261-268. doi: 10.4110/in.2017.17.4.261. Epub 2017 Aug 11.
Tumor necrosis factor-α (TNF-α) induces serum amyloid A (SAA) 3 among acute-phase proteins in mouse granulosa cells by activating NF-κB signaling via p55 TNF-α receptor type 1. However, the localization of SAA3 within the ovary is unknown. Here we investigated ovarian localization of SAA3 in a mouse ovulation model and in response to IL-1β, a proinflammatory mediator. For the ovulation model, equine chorionic gonadotropin (eCG; 2.5 IU) was administered to mice subcutaneously (sc) to stimulate follicular development on day 25 of age and then 50 h after eCG, human chorionic gonadotropin (hCG; 2.5 IU) was administered sc to induce ovulation. The mouse ovulation model was characterized by the localization of CYP19 mRNA expression to granulosa layers of larger follicles. SAA3 mRNA, determined by hybridization, was broadly expressed throughout the whole ovary. Granulosa layers and small follicles expressed higher SAA3 mRNA compared to thecal-interstitial layers and large follicles, respectively. Interestingly, atretic follicles contained cells expressing intense SAA3 mRNA. After ovulation, SAA3 mRNA expression was intensely evident in ruptured follicles and corpora lutea (CL). The intraperitoneal administration of IL-1β revealed the intense and extensive appearance of specific cells expressing SAA3 mRNA around follicles and in CL. In addition, Gene Expression Omnibus (GEO) database analysis supported expression pattern of SAA3 mRNA observed in mouse ovulation model. Taken together, SAA3 was broadly distributed through the whole ovary, but intensely expressed in atretic follicles and CL. Furthermore, proinflammatory mediators could trigger the intense appearance of SAA3 around follicles and in CL.
肿瘤坏死因子-α(TNF-α)通过激活经由1型p55 TNF-α受体的NF-κB信号通路,在小鼠颗粒细胞的急性期蛋白中诱导血清淀粉样蛋白A(SAA)3。然而,SAA3在卵巢内的定位尚不清楚。在此,我们在小鼠排卵模型中以及对促炎介质白细胞介素-1β(IL-1β)的反应中研究了SAA3在卵巢中的定位。对于排卵模型,在25日龄时皮下(sc)给小鼠注射马绒毛膜促性腺激素(eCG;2.5 IU)以刺激卵泡发育,然后在eCG注射50小时后,皮下注射人绒毛膜促性腺激素(hCG;2.5 IU)以诱导排卵。小鼠排卵模型的特征在于CYP19 mRNA表达定位于较大卵泡的颗粒层。通过杂交测定的SAA3 mRNA在整个卵巢中广泛表达。与卵泡膜-间质层和大卵泡相比,颗粒层和小卵泡分别表达更高的SAA3 mRNA。有趣的是,闭锁卵泡含有表达强烈SAA3 mRNA的细胞。排卵后,SAA3 mRNA表达在破裂卵泡和黄体(CL)中明显增强。腹腔注射IL-1β显示在卵泡周围和CL中出现强烈且广泛的表达SAA3 mRNA的特异性细胞。此外,基因表达综合数据库(GEO)分析支持在小鼠排卵模型中观察到的SAA3 mRNA表达模式。综上所述,SAA3广泛分布于整个卵巢,但在闭锁卵泡和CL中强烈表达。此外,促炎介质可引发卵泡周围和CL中SAA3的强烈出现。