Extra villous trophoblast-derived PDL1 can ameliorate macrophage inflammation and promote immune adaptation associated with preeclampsia.

INTRODUCTION: Severe preeclampsia (sPE) is a systemic syndrome that may originate from chronic inflammation. Maintaining maternal-fetal hemostasis by the co-inhibitory molecule programmed death ligand 1 (PDL1) can be favorable for ameliorating inflammation from immune cells. Apart from programmed death 1 (PD1) expression, decidual macrophages (dMs) produce inflammatory cytokines, in response to cells which express PDL1. However, strong evidence is lacking regarding whether the PDL1/PD1 interaction between trophoblasts and decidual macrophages affects inflammation during sPE development. METHODS: To determine whether the trophoblast-macrophage crosstalk via the PDL1/PD1 axis modulates the inflammatory response in sPE-like conditions, at first, maternal-fetal tissues from sPE and normal patients were collected, and the PDL1/PD1 distribution was analyzed by Western blot, immunohistochemistry/ immunofluorescence and flow cytometry. Next, a coculture system was established and flow cytometry was used to identify how PDL1 was involved in macrophage-related inflammation under hypoxic stress. Transcriptional analysis was performed to clarify the inflammation-associated pathway induced by the PDL1/PD1 interaction. Finally, the Nω-nitro-L-arginine methyl ester hydrochloride (L-NAME) mouse model was used to examine the effect of PDL1 on macrophage-related inflammation by measuring PE-like symptoms. RESULTS: In maternal-fetal tissue from sPE patients, placental extravillous trophoblasts (EVTs) and dMs had a surprisingly increase of PDL1 and PD1 expression, respectively, accompanied by a higher percentage of CD68 +CD86 + dMs. In vitro experiments showed that trophoblast-derived PDL1 under hypoxia interacted with PD1 on CD14 +CD80 +macrophages, leading to suppression of inflammation through the TNFα-p38/NFκB pathway. Accordingly, the PE-like mouse model showed a reversal of PE-like symptoms and a reduced F4/80 + CD86 + macrophage percentage in the uterus in response to recombinant PDL1 protein administration, indicating the protective effect of PDL1. DISCUSSION: Our results initially explained an immunological adaptation of trophoblasts under placental hypoxia, although this protection was insufficient. Our findings suggest the possible capacity of modulating PDL1 expression as a potential therapeutic strategy to target the inflammatory response in sPE.

LINC00511 promotes proliferation and invasion by sponging miR-515-5p in gastric cancer.

BACKGROUND: Long non-coding RNAs (lncRNAs) are known to be involved in tumorigenesis. The functions of LINC00511 in gastric cancer are poorly understood. METHODS: Quantitative RT-PCR was performed to investigate the levels of LINC00511 in gastric cancer tissues and cell lines. CCK-8, flow cytometry, wound-healing and Transwell assays were performed to examine cellular functions. The underlying regulatory mechanisms of LINC00511 in gastric cancer progression were determined using luciferase reporter and RIP assays. RESULTS: LINC00511 levels were significantly higher in gastric cancer tissues and cell lines than in normal samples. The high expression of LINC00511 in gastric cancer patient samples positively correlated with advanced clinical characters and poor prognosis. Depleting LINC00511 reduced tumor cell proliferation, migration and invasion, slowed tumor growth, and accelerated cell apoptosis. Our mechanistic study results indicated that LINC00511 promotes gastric cancer progression in a miR-515-5p-dependent manner. CONCLUSION: We established that LINC00511 may contribute to the proliferation and invasion of gastric cancer cells by modulating miR-515-5p, indicating that LINC00511 may be a potential molecular target for the development of anti-cancer drugs.