Lipopolysaccharide initiates inflammation in bovine granulosa cells via the TLR4 pathway and perturbs oocyte meiotic progression in vitro.
Lipopolysaccharide initiates inflammation in bovine granulosa cells via the TLR4 pathway and perturbs oocyte meiotic progression in vitro.
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DOI：
10.1210/en.2011-1124
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发表时间：
2011-12
期刊：
影响因子：
4.8
通讯作者：
Sheldon IM
中科院分区：
文献类型：
--
作者：
Bromfield JJ;Sheldon IM
生殖道或乳腺感染革兰氏阴性菌会扰乱牛的卵巢功能、卵泡生长和繁殖力。我们假设来自革兰氏阴性细菌的脂多糖（LPS）刺激卵巢颗粒细胞的炎症反应，该反应由TLR 4介导。本研究检测了牛卵巢颗粒细胞对病原体相关分子模式（PAMPs）启动炎症反应的能力，并确定了随后对卵母细胞体外成熟的影响。颗粒细胞引起对PAMPs（LPS、脂磷壁酸、肽聚糖或Pam 3CSK 4）的炎症反应，并以时间和剂量依赖性方式积累细胞因子IL-6和趋化因子IL-8。颗粒细胞对LPS反应强烈，TLR信号成分p38和ERK迅速磷酸化，IL 6和IL 8 mRNA表达增加，尽管p65核转位不明显。用siRNA靶向TLR 4，减弱了颗粒细胞响应于LPS的IL-6积累。颗粒细胞的内分泌功能受FSH调节，但FSH也增强了对LPS的反应性，增加了IL-6和IL-8的积累。此外，LPS刺激卵丘-卵母细胞复合体（COCs）的IL-6分泌和扩增，并增加减数分裂阻滞和生殖囊泡破裂失败的比率。总之，牛颗粒细胞通过TLR 4途径启动对LPS的先天免疫应答，导致炎症和减数分裂能力的扰动。
Infections of the reproductive tract or mammary gland with Gram-negative bacteria perturb ovarian function, follicular growth and fecundity in cattle. We hypothesised that lipopolysaccharide (LPS) from Gram-negative bacteria stimulates an inflammatory response by ovarian granulosa cells that is mediated by TLR4. The present study tested the capacity of bovine ovarian granulosa cells to initiate an inflammatory response to pathogen associated molecular patterns (PAMPs), and determined subsequent effects on the in vitro maturation of oocytes. Granulosa cells elicited an inflammatory response to PAMPs (LPS, lipoteichoic acid, peptidoglycan or Pam3CSK4) with accumulation of the cytokine IL-6, and the chemokine IL-8, in a time- and dose-dependent manner. Granulosa cells responded acutely to LPS with rapid phosphorylation of TLR signaling components, p38 and ERK, and increased expression of IL6 and IL8 mRNA, although nuclear translocation of p65 was not evident. Targeting TLR4 with siRNA, attenuated granulosa cell accumulation of IL-6 in response to LPS. Endocrine function of granulosa cells is regulated by FSH, but here FSH also enhanced responsiveness to LPS, increasing IL-6 and IL-8 accumulation. Furthermore, LPS stimulated IL-6 secretion and expansion by cumulus-oocyte complexes (COCs), and increased rates of meiotic arrest and germinal vesicle breakdown failure. In conclusion, bovine granulosa cells initiate an innate immune response to LPS via the TLR4 pathway leading to inflammation and to perturbation of meiotic competence.
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DOI：
10.1530/rep-07-0229
发表时间：
2007-11
期刊：
Reproduction (Cambridge, England)
影响因子：
--
作者：
Herath S;Williams EJ;Lilly ST;Gilbert RO;Dobson H;Bryant CE;Sheldon IM
通讯作者：
Sheldon IM
影响因子：
3.5
作者：
Hertl, J. A.;Groehn, Y. T.;Schukken, Y. H.
通讯作者：
Schukken, Y. H.
DOI：
10.1046/j.1365-201x.2001.00813.x
发表时间：
2001-05-01
期刊：
ACTA PHYSIOLOGICA SCANDINAVICA
影响因子：
--
作者：
Besnard, N;Horne, EAL;Whitehead, SA
通讯作者：
Whitehead, SA
影响因子：
6.1
作者：
Bromfield, J. J.;Coticchio, G.;Albertini, D. F.
通讯作者：
Albertini, D. F.
影响因子：
3.6
作者：
BRANNSTROM, M;MAYRHOFER, G;ROBERTSON, SA
通讯作者：
ROBERTSON, SA