Department of Physiology, Faculty of Veterinary Medicine, Erciyes University, Turkey.
Department of Obstetrics and Gynecology, Faculty of Veterinary Medicine, Erciyes University, Turkey.
Reproduction. 2024 Sep 11;168(4). doi: 10.1530/REP-23-0368. Print 2024 Oct 1.
Activation of TLR2/TLR1 alters in vitro formation of capillary-like structures and induces inflammatory processes in ovine luteal endothelial (OLENDO) cells.
Postpartum bacterial infections of the uterus affect uterine physiology and ovarian activity, causing fertility problems. The outer membrane component of Gram-negative bacteria, lipopolysaccharide, is involved in the initiation of the local inflammatory processes, and other bacterial toxins, particularly lipopeptides, have also been shown to be potent cytokine inducers, acting via Toll-like receptor-2 (TLR2). However, the possible adverse effects of TLR2 on ovarian and luteal activities have not yet been investigated in depth. The strong expression of TLR2 in the blood vessels of the corpus luteum led us to hypothesize that TLR2 activation might participate in the disruption of luteal vascular functionality. Therefore, we analyzed the effects of Pam3CSK4 (Pam3CysSerLys4), a synthetic triacylated lipopeptide and TLR2/TLR1 ligand, on the functionality of gap junctional intercellular communication (GJIC), endothelial cell invasion, and in vitro capillary-like network formation in an immortalized ovine luteal endothelial (OLENDO) cell line. Pam3CSK4 treatment of OLENDO cells disrupted in vitro tube formation but had no effect on GJIC or migration of OLENDO cells. Furthermore, Pam3CSK4 induced the expression of NFKB, IL6, and IL8 in OLENDO cells. Additionally, the basal availability of TLRs (TLR1-10) and TLR co-receptors (MYD88, LY96/MD2, and CD14) in OLENDO cells was confirmed by conventional PCR. Finally, the activation of TLR2/TLR1 appears to alter in vitro formation of capillary-like structures and induce inflammatory processes in OLENDO cells.
产后子宫细菌感染会影响子宫生理学和卵巢活性，导致生育问题。革兰氏阴性菌的外膜成分脂多糖（LPS）参与了局部炎症过程的启动，其他细菌毒素，特别是脂肽，也被证明是有效的细胞因子诱导剂，通过 Toll 样受体 2（TLR2）发挥作用。然而，TLR2 对卵巢和黄体活动的可能不利影响尚未得到深入研究。TLR2 在黄体血管中的强烈表达使我们假设 TLR2 的激活可能参与了黄体血管功能的破坏。因此，我们分析了 Pam3CSK4（Pam3CysSerLys4）对缝隙连接细胞间通讯（GJIC）、内皮细胞侵袭和体外毛细血管样网络形成功能的影响，Pam3CSK4 是一种合成的三酰化脂肽和 TLR2/TLR1 配体，在永生化绵羊黄体内皮（OLENDO）细胞系中。Pam3CSK4 处理 OLENDO 细胞破坏了体外管形成，但对 GJIC 或 OLENDO 细胞迁移没有影响。此外，Pam3CSK4 诱导 OLENDO 细胞中 NFKB、IL6 和 IL8 的表达。此外，通过常规 PCR 证实了 OLENDO 细胞中 TLRs（TLR1-10）和 TLR 共受体（MYD88、LY96/MD2 和 CD14）的基础可用性。最后，TLR2/TLR1 的激活似乎改变了 OLENDO 细胞中体外毛细血管样结构的形成，并诱导了炎症过程。
