title: Neuromedin B and its receptor influence the activity of myometrial primary cells in vitro through regulation of Il6 expression via the Rela/p65 pathway in mice.
abstract: The neuromedin B receptor (Nmbr) is an important physiological regulator of spontaneous activities and stress responses through different cascades as well as its autocrine and paracrine effects. Previous studies have revealed that neuromedin B (Nmb) and its receptor signal via the Rela (also known as p65)/Il6 pathway in a mouse model of pregnancy. This study investigated the mechanism of Nmbr signaling via the Rela/p65-Il6 pathway and regulation of the concentration of intracellular free calcium ([Ca(2+)](i)) during the onset of labor in primary mouse myometrial cell cultures isolated from mice in term labor. Data demonstrated Nmbr agonist-mediated upregulation of the DNA binding activity of Rela/p65, Il6 expression, and [Ca(2+)](i) in a concentration-dependent manner. Furthermore, a significant correlation was observed between DNA binding activity of Rela/p65 and Il6 expression. Moreover, this up-regulation was blocked by Nmbr and Rela/p65 knockdown, achieved by RNA interference (RNAi) technology. No significant differences were identified in the inhibition of Il6 expression as a result of Nmbr or Rela/p65 knockdown. However, significant differences were observed between the [Ca(2+)](i) in Rela/p65-specific group and that in the Nmbr-specific small interfering RNA (siRNA)-treated groups. These data demonstrated that the Nmb/Nmbr interaction in pregnant myometrial primary cells in vitro predominantly influenced uterine activity through regulation of Il6 expression via the Rela/p65 pathway, although the effects of Nmbr on [Ca(2+)](i) involved several pathways that remain to be elucidated.
authors.affiliation: Department of Obstetrics and Gynecology, Xiangya Hospital, Central South University, Hunan, Changsha, China. weishezhang2003@yahoo.com.cn
authors.forename: Wei-She
authors.initials: WS
authors.lastname: Zhang
authors.forename: Kui-Lin
authors.initials: KL
authors.lastname: Fei
authors.forename: Mei-Ting
authors.initials: MT
authors.lastname: Wu
authors.forename: Xin-Hua
authors.initials: XH
authors.lastname: Wu
authors.forename: Qing-Hua
authors.initials: QH
authors.lastname: Liang
mesh_terms: D000818:Animals; D002118:Calcium / Q000502:physiology; D002478:Cells, Cultured; D005260:Female; D015850:Interleukin-6 / Q000096:biosynthesis*; D007745:Labor Onset / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D009215:Myometrium / Q000502:physiology*; D015287:Neurokinin B / Q000031:analogs & derivatives* / Q000502:physiology; D011247:Pregnancy; D034622:RNA Interference / Q000502:physiology; D018004:Receptors, Bombesin / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology; D051996:Transcription Factor RelA / Q000502:physiology*; D015854:Up-Regulation / Q000502:physiology
chemical_list: D015850:Interleukin-6; D018004:Receptors, Bombesin; C498144:Rela protein, mouse; D051996:Transcription Factor RelA; D015287:Neurokinin B; C038393:neuromedin B; D002118:Calcium