The Bradykinin System Contributes to the Regulation of Prostaglandin-Endoperoxide Synthase 2 Expression in Human Amnion Fibroblasts: Implications for Term and Preterm Birth

Ni, Xiao-Tian; Wang, Wangsheng; Liu, Yun; Lin, Yi-Kai; Zhang, Fan; Lei, Wen-Jia; Ling, Liuyi; Pan, Fan; Zhu, Yanan; Li, Meng-die; Duan, Tao; Liu, Ming; Sun, Kang

doi:10.3389/fendo.2022.873727

Cited by 4 publications

(6 citation statements)

References 51 publications

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“…Here, in this study, we also demonstrated that MAPK and NF-κB pathways underpinned the IL-33 actions in ovarian CAFs. In mammals, MAPKs could be classified into three primary subfamilies, namely, JNK, ERK, and p38, which have been demonstrated to be associated with both infection and non-infection-induced inflammatory responses (Rodriguez-Barbero et al, 2006;Arthur and Ley, 2013;Ni et al, 2022). In this regard, we found that all three MAPKs were involved in the induction of IL-6, PGE2, and IL-1β expressions by IL-33 in ovarian CAFs, further indicating a crucial role of MAPKs in the inflammatory responses of the TM at OvC.…”

Section: Discussionmentioning

confidence: 99%

Identification of novel candidate targets for suppressing ovarian cancer progression through IL-33/ST2 axis components using the system biology approach

Reivan Ortiz,

Ciongradi,

Chaitanya

et al. 2023

Front. Mol. Biosci.

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Background: Cancer-associated fibroblasts (CAFs) of ovarian cancer (OvC) are the most prevalent element of the tumor microenvironment (TM). By promoting angiogenesis, immunological suppression, and invasion, CAFs speed up the growth of tumors by changing the extracellular matrix’s structure and composition and/or initiating the epithelial cells (EPT). IL-33/ST2 signaling has drawn a lot of attention since it acts as a pro-tumor alarmin and encourages spread by altering TM.Methods: Differentially expressed genes (DEGs) of the OvC tumor microenvironment were found in the GEO database, qRT-PCR, western blotting, and immunohistochemistry, and their presence and changes in healthy and tumor tissue content were examined. Primary cultures of healthy fibroblasts and CAFs obtained from healthy and tumor tissues retrieved from OvC samples were used for in vitro and in vivo investigations. Cultured primary human CAFs were utilized to investigate the regulation and the IL-33/ST2 axis role in the inflammation reactions.Results: Although ST2 and IL-33 expression was detected in both epithelial (EPT) and fibroblast cells of ovarian cancer, they are more abundant in CAFs. Lipopolysaccharides, serum amyloid A1, and IL-1β, the inflammatory mediators, could all induce IL-33 expression through NF-κB activation in human CAFs. In turn, via the ST2 receptor, IL-33 affected the production of IL-6, IL-1β, and PTGS2 in human CAFs via the MAPKs-NF-κB pathway.Conclusion: Our findings suggest that IL-33/ST2 is affected by the interaction of CAFs and epithelial cells inside the tumor microenvironment. Activation of this axis leads to increased expression of inflammatory factors in tumor CAFs and EPT cells. Therefore, targeting the IL-33/ST2 axis could have potential value in the prevention of OvC progression.

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Section: Discussionmentioning

confidence: 99%

Identification of novel candidate targets for suppressing ovarian cancer progression through IL-33/ST2 axis components using the system biology approach

Reivan Ortiz,

Ciongradi,

Chaitanya

et al. 2023

Front. Mol. Biosci.

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“…Des-Arg9-BK enhances angiogenesis under inflammatory conditions and the migration as well as invasion of cancer cells. 15,16 Moreover, MMD affects the blood-brain barrier (BBB), a complex network of specialized cells essential for maintaining a stable environment for the brain. BBB protects the brain from harmful substances in the blood.…”

Section: Backg Rou N Dmentioning

confidence: 99%

“…BK enhances the proliferative and migratory ability of ECs and stimulates new blood vessel formation in vivo. Des‐Arg9‐BK enhances angiogenesis under inflammatory conditions and the migration as well as invasion of cancer cells 15,16 …”

Section: Introductionmentioning

confidence: 99%

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Bradykinin‐bradykinin receptor (B1R) signalling is involved in the blood–brain barrier disruption in moyamoya disease

Wang,

Sun,

et al. 2023

J Cellular Molecular Medi

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Moyamoya disease (MMD) is a rare disorder of the cerebrovascular system. It is a steno‐occlusive disease that involves angiogenesis and blood–brain barrier (BBB) disruption. Bradykinin (BK), its metabolite des‐Arg9‐BK, and receptor (B1R) affect angiogenesis and BBB integrity. In this study, we aimed to investigate the changes in BK, B1R and des‐Arg9‐BK levels in the serum and brain tissues of patients with MMD and explore the underlying mechanism of these markers in MMD. We obtained the serum samples and superficial temporal artery (STA) tissue of patients with MMD from the Department of Neurosurgery of the Jining First People's Hospital. First, we measured BK, des‐Arg9‐BK and B1R levels in the serum of patients by means of ELISA. Next, we performed immunofluorescence to determine B1R expression in STA tissues. Finally, we determined the underlying mechanism through Western blot, angiogenesis assay, immunofluorescence, transendothelial electrical resistance and transcytosis assays. Our results demonstrated a significant increase in the BK, des‐Arg9‐BK and B1R levels in the serum of patients with MMD compared to healthy controls. Furthermore, an increase in the B1R expression level was observed in the STA tissues of patients with MMD. BK and des‐Arg9‐BK could promote the migratory and proliferative abilities of bEnd.3 cells and inhibited the formation of bEnd.3 cell tubes. In vitro BBB model showed that BK and des‐Arg9‐BK could reduce claudin‐5, ZO‐1 and occluding expression and BBB disruption. To the best of our knowledge, our results show an increase in BK and B1R levels in the serum and STA tissues of patients with MMD. BK and Des‐Arg9‐BK could inhibit angiogenesis, promote migratory and proliferative capacities of cells, and disrupt BBB integrity. Therefore, regulating BK, des‐Arg9‐BK and B1R levels in the serum and the brain could be potential strategies for treating patients with MMD.

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“…The amnion layer of the fetal membranes not only determines the tensile strength of the fetal membranes but also harbors a myriad of inflammatory signaling molecules (Menon et al 2020 ; Oyen et al 2006 ; Wang et al 2018 ). We and others have demonstrated that mesenchymal cells of the amnion produce a large amount of prostaglandins and pro-inflammatory cytokines (Keelan et al 1997 , 2003 ; Li et al 2017 ; Ni et al 2022 ; Okazaki et al 1981 ; Zhang et al 2017 ). Therefore, understanding the expression and regulation of pro-inflammatory signaling molecules in amnion mesenchymal cells may help further understand the unresolved mechanisms of human parturition.…”

Section: Introductionmentioning

confidence: 96%

IL-33/ST2 axis of human amnion fibroblasts participates in inflammatory reactions at parturition

Lei

Zhang

Lin

et al. 2023

Mol Med

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Background Inflammation of the fetal membranes is an indispensable event of labor onset at both term and preterm birth. Interleukin-33 (IL-33) is known to participate in inflammation via ST2 (suppression of tumorigenicity 2) receptor as an inflammatory cytokine. However, it remains unknown whether IL-33/ST2 axis exists in human fetal membranes to promote inflammatory reactions in parturition. Methods The presence of IL-33 and ST2 and their changes at parturition were examined with transcriptomic sequencing, quantitative real-time polymerase chain reaction, Western blotting or immunohistochemistry in human amnion obtained from term and preterm birth with or without labor. Cultured primary human amnion fibroblasts were utilized to investigate the regulation and the role of IL-33/ST2 axis in the inflammation reactions. A mouse model was used to further study the role of IL-33 in parturition. Results Although IL-33 and ST2 expression were detected in both epithelial and fibroblast cells of human amnion, they are more abundant in amnion fibroblasts. Their abundance increased significantly in the amnion at both term and preterm birth with labor. Lipopolysaccharide, serum amyloid A1 and IL-1β, the inflammatory mediators pertinent to labor onset, could all induce IL-33 expression through NF-κB activation in human amnion fibroblasts. In turn, via ST2 receptor, IL-33 induced the production of IL-1β, IL-6 and PGE2 in human amnion fibroblasts via the MAPKs-NF-κB pathway. Moreover, IL-33 administration induced preterm birth in mice. Conclusion IL-33/ST2 axis is present in human amnion fibroblasts, which is activated in both term and preterm labor. Activation of this axis leads to increased production of inflammatory factors pertinent to parturition, and results in preterm birth. Targeting the IL-33/ST2 axis may have potential value in the treatment of preterm birth.

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The Bradykinin System Contributes to the Regulation of Prostaglandin-Endoperoxide Synthase 2 Expression in Human Amnion Fibroblasts: Implications for Term and Preterm Birth

Cited by 4 publications

References 51 publications

Identification of novel candidate targets for suppressing ovarian cancer progression through IL-33/ST2 axis components using the system biology approach

Identification of novel candidate targets for suppressing ovarian cancer progression through IL-33/ST2 axis components using the system biology approach

Bradykinin‐bradykinin receptor (B1R) signalling is involved in the blood–brain barrier disruption in moyamoya disease

IL-33/ST2 axis of human amnion fibroblasts participates in inflammatory reactions at parturition

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