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The Potential Therapeutic Role of miR-223 in Bovine Endometritis by Targeting the NLRP3 Inflammasome.

ABSTRACT: Bovine endometritis affects milk production and reproductive performance in dairy cows and causes serious economic loss. The underlying molecular mechanisms or signaling pathways of bovine endometritis remain unclear. In this study, we attempted to determine the expression mechanism of mir-223 in endometritis of dairy cows and evaluate its potential therapeutic value. We first confirmed that there was an increased level of miR-223 in endometritis, and then, an LPS-induced bovine endometrial epithelial cell (BEND) line was used to mimic the inflammatory model in vitro. Our data showed that activation of NF-?B promoted the transcription of miR-223, thus inhibiting activation of the inflammatory mediator NLRP3 and its mediation of IL-1? production to protect against inflammatory damage. Meanwhile, in vivo studies showed that inhibition of mir-223 resulted in an enhanced pathology of mice during LPS-induced endometritis, while overexpression of mir-223 attenuated the inflammatory conditions in the uterus. In summary, our study highlights that miR-223 serves both to constrain the level of NLRP3 activation and to act as a protective factor in the inflammatory response and thus provides a future novel therapeutic modality for active flares in cow endometritis and other inflammatory diseases.

SUBMITTER: Zhao G

PROVIDER: S-EPMC6113393 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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The Potential Therapeutic Role of miR-223 in Bovine Endometritis by Targeting the NLRP3 Inflammasome.

Zhao Gan G Jiang Kangfeng K Yang Yaping Y Zhang Tao T Wu Haichong H Shaukat Aftab A Qiu Changwei C Deng Ganzhen G

Frontiers in immunology 20180822

Bovine endometritis affects milk production and reproductive performance in dairy cows and causes serious economic loss. The underlying molecular mechanisms or signaling pathways of bovine endometritis remain unclear. In this study, we attempted to determine the expression mechanism of mir-223 in endometritis of dairy cows and evaluate its potential therapeutic value. We first confirmed that there was an increased level of miR-223 in endometritis, and then, an LPS-induced bovine endometrial epit ...[more]

PMID: 30186287

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Project description:IntroductionDysregulation of NLRP3 inflammasome complex formation can promote chronic inflammation by increased release of IL-1β. However, the effect of NLRP3 complex formation on tumor progression remains controversial. Therefore, we sought to determine the effect of NLRP3 modulation on the growth of the different types of cancer cells, derived from lung, breast, and prostate cancers as well as neuroblastoma and glioblastoma in-vitro.MethodThe effect of Caspase 1 inhibitor (VX765) and combination of LPS/Nigericin on NLRP3 inflammasome activity was analyzed in A549 (lung cancer), MCF-7 (breast cancer), PC3 (prostate cancer), SH-SY5Y (neuroblastoma), and U138MG (glioblastoma) cells. Human fibroblasts were used as control cells. The effect of VX765 and LPS/Nigericin on NLRP3 expression was analyzed using western blot, while IL-1β and IL-18 secretion was detected by ELISA. Tumor cell viability and progression were determined using Annexin V, cell proliferation assay, LDH assay, sphere formation assay, transmission electron microscopy, and a multiplex cytokine assay. Also, angiogenesis was investigated by a tube formation assay. VEGF and MMPs secretion were detected by ELISA and a multiplex assay, respectively. Statistical analysis was done using one-way ANOVA with Tukey's analyses and Kruskal-Wallis one-way analysis of variance.ResultsLPS/Nigericin increased NRLP3 protein expression as well as IL-1β and IL-18 secretion in PC3 and U138MG cells compared to A549, MCF7, SH-SY5Y cells, and fibroblasts. In contrast, MIF expression was commonly found upregulated in A549, PC3, SH-SY5Y, and U138MG cells and fibroblasts after Nigericin treatment. Nigericin and a combination of LPS/Nigericin decreased the cell viability and proliferation. Also, LPS/Nigericin significantly increased tumorsphere size in PC3 and U138MG cells. In contrast, the sphere size was reduced in MCF7 and SH-SY5Y cells treated with LPS/Nigericin, while no effect was detected in A549 cells. VX765 increased secretion of CCL24 in A549, MCF7, PC3, and fibroblasts as well as CCL11 and CCL26 in SH-SY5Y cells. Also, VX765 significantly increased the production of VEGF and MMPs and stimulated angiogenesis in all tumor cell lines.DiscussionOur data suggest that NLRP3 activation using Nigericin could be a novel therapeutic approach to control the growth of tumors producing a low level of IL-1β and IL-18.

Dataset Information

The Potential Therapeutic Role of miR-223 in Bovine Endometritis by Targeting the NLRP3 Inflammasome.

Publications

The Potential Therapeutic Role of miR-223 in Bovine Endometritis by Targeting the NLRP3 Inflammasome.

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