Register      Login
Reproduction, Fertility and Development Reproduction, Fertility and Development Society
Vertebrate reproductive science and technology
RESEARCH ARTICLE

Ssc-novel-miR-106-5p reduces lipopolysaccharide-induced inflammatory response in porcine endometrial epithelial cells by inhibiting the expression of the target gene mitogen-activated protein kinase kinase kinase 14 (MAP3K14)

Yu Lian A , Yu Hu A , Lu Gan A , Yuan-Nan Huo A , Hong-Yan Luo B and Xian-Zhong Wang https://orcid.org/0000-0002-4540-1540 A C
+ Author Affiliations
- Author Affiliations

A Chongqing Key Laboratory of Forage and Herbivore, College of Animal Science and Technology, Southwest University, Beibei, Chongqing 400716, P. R. China.

B College of Resource and Environment, Southwest University, Beibei, Chongqing 400716, P. R. China.

C Corresponding author. Email: xianzhong_wang@aliyun.com

Reproduction, Fertility and Development 31(10) 1616-1627 https://doi.org/10.1071/RD19097
Submitted: 6 December 2018  Accepted: 12 May 2019   Published: 27 June 2019

Abstract

As an important gram-negative bacterial outer membrane component, lipopolysaccharide (LPS) plays an important role in bacterial-induced endometritis in sows. However, how LPS induces endometritis is unclear. We stimulated sow endometrial epithelial cells (EECs) with LPS and detected cell viability and tumour necrosis factor-α (TNF-α) and interleukin-1 (IL-1) secretion. LPS affected EEC viability and TNF-α and IL-1 secretion in a dose-dependent manner. LPS induced differential expression in 10 of 393 miRNAs in the EECs (downregulated, nine; upregulated, one). MicroRNA (miRNA) high-throughput sequencing of the LPS-induced EECs plus bioinformatics analysis and the dual-luciferase reporter system revealed a novel miRNA target gene: mitogen-activated protein kinase kinase kinase 14 (MAP3K14). Ssc-novel-miR-106-5p mimic, inhibitor and the nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha (IκBα) phosphorylation inhibitor Bay11–7085 were used to detect EEC nuclear factor-κB phosphorylation levels (p-NF-κB) and TNF-α and IL-1 secretion. MiR-106-5p mimic downregulated MAP3K14 mRNA and protein expression levels, inhibited p-NF-κB levels and decreased IL-1 and TNF-α secretion, whereas miR-106-5p inhibitor had the opposite effect. Bay11–7085 inhibited p-NF-κB expression and TNF-α and IL-1 secretion. These results suggest that LPS downregulates ssc-novel-miR-106-5p expression in sow EECs to increase MAP3K14 expression, which increases p-NF-κB to promote IL-1 and TNF-α secretion.

Additional keywords: IL-1, NF-κB, Sus scrofa domestica, TNF-α.


References

Aflatoonian, R., and Fazeli, A. (2008). Toll-like receptors in female reproductive tract and their menstrual cycle dependent expression. J. Reprod. Immunol. 77, 7–13.
Toll-like receptors in female reproductive tract and their menstrual cycle dependent expression.Crossref | GoogleScholarGoogle Scholar | 17493683PubMed |

Amos, M. R., Healey, G. D., Goldstone, R. J., Mahan, S. M., Düvel, A., Schuberth, H. J., and Smith, D. G. E. (2014). Differential endometrial cell sensitivity to a cholesterol-dependent cytolysin links Trueperella pyogenes to uterine disease in cattle. Biol. Reprod. 90, 54.
Differential endometrial cell sensitivity to a cholesterol-dependent cytolysin links Trueperella pyogenes to uterine disease in cattle.Crossref | GoogleScholarGoogle Scholar | 24478394PubMed |

Barnes, P. J., and Karin, M. (1997). Nuclear factor-κB – a pivotal transcription factor in chronic inflammatory diseases. N. Engl. J. Med. 336, 1066–1071.
Nuclear factor-κB – a pivotal transcription factor in chronic inflammatory diseases.Crossref | GoogleScholarGoogle Scholar | 9091804PubMed |

Brasier, A. R. (2006). The NF-κB regulatory network. Cardiovasc. Toxicol. 6, 111–130.
The NF-κB regulatory network.Crossref | GoogleScholarGoogle Scholar | 17303919PubMed |

Cagiola, M., Giulio, S., Miriam, M., Katia, F., Paola, P., Macrì, A., and Pasquali, P. (2006). In vitro down regulation of proinflammatory cytokines induced by LPS tolerance in pig CD14+ cells. Vet. Immunol. Immunopathol. 112, 316–320.
In vitro down regulation of proinflammatory cytokines induced by LPS tolerance in pig CD14+ cells.Crossref | GoogleScholarGoogle Scholar | 16740319PubMed |

Chang, F., Steelman, L., Lee, J., Shelton, J., Navolanic, P., Blalock, W., and McCubrey, J. (2003). Signal transduction mediated by the Ras/Raf/MEK/ERK pathway from cytokine receptors to transcription factors: potential targeting for therapeutic intervention. Leukemia 17, 1263–1293.
Signal transduction mediated by the Ras/Raf/MEK/ERK pathway from cytokine receptors to transcription factors: potential targeting for therapeutic intervention.Crossref | GoogleScholarGoogle Scholar | 12835716PubMed |

Chanrot, M., Blomqvist, G., Guo, Y., Ullman, K., Juremalm, M., Bage, R., and Humblot, P. (2017). Bovine herpes virus type 4 alters TNF-α and IL-8 profiles and impairs the survival of bovine endometrial epithelial cells. Reprod. Biol. 17, 225–232.
Bovine herpes virus type 4 alters TNF-α and IL-8 profiles and impairs the survival of bovine endometrial epithelial cells.Crossref | GoogleScholarGoogle Scholar | 28546031PubMed |

Chen, C. Z., Li, L., Lodish, H. F., and Bartel, D. P. (2004). MicroRNAs modulate hematopoietic lineage differentiation. Science 303, 83–86.
MicroRNAs modulate hematopoietic lineage differentiation.Crossref | GoogleScholarGoogle Scholar | 14657504PubMed |

Chen, X., Fan, Z., McGee, W., Chen, M., Kong, R., Wen, P., and Zhu, L. (2018). TDP-43 regulates cancer-associated microRNAs. Protein Cell 9, 848–866.
TDP-43 regulates cancer-associated microRNAs.Crossref | GoogleScholarGoogle Scholar | 28952053PubMed |

Cheng, Z., Elmes, M., Kirkup, S. E., Chin, E. C., Abayasekara, D. R. E., and Wathes, D. C. (2005). The effect of a diet supplemented with the n-6 polyunsaturated fatty acid linoleic acid on prostaglandin production in early- and late-pregnant ewes. J. Endocrinol. 184, 165–178.
The effect of a diet supplemented with the n-6 polyunsaturated fatty acid linoleic acid on prostaglandin production in early- and late-pregnant ewes.Crossref | GoogleScholarGoogle Scholar | 15642793PubMed |

Choudhary, S., Boldogh, S., Garofalo, R., Jamaluddin, M., and Brasier, A. R. (2005). Respiratory syncytial virus influences NF-kappaB-dependent gene expression through a novel pathway involving MAP3K14/NIK expression and nuclear complex formation with NF-kappaB2. J. Virol. 79, 8948–8959.
Respiratory syncytial virus influences NF-kappaB-dependent gene expression through a novel pathway involving MAP3K14/NIK expression and nuclear complex formation with NF-kappaB2.Crossref | GoogleScholarGoogle Scholar | 15994789PubMed |

Conti, B. J., Santiago, K. B., Cardoso, E. O., Freire, P. P., Carvalho, R. F., Golim, M. A., and Sforcin, J. M. (2016). Propolis modulates miRNAs involved in TLR-4 pathway, NF-κB activation, cytokine production and in the bactericidal activity of human dendritic cells. J. Pharm. Pharmacol. 68, 1604–1612.
Propolis modulates miRNAs involved in TLR-4 pathway, NF-κB activation, cytokine production and in the bactericidal activity of human dendritic cells.Crossref | GoogleScholarGoogle Scholar | 27714813PubMed |

Crisafulli, C., Galuppo, M., and Cuzzocrea, S. (2009). Effects of genetic and pharmacological inhibition of TNF-alpha in the regulation of inflammation in macrophages. Pharmacol. Res. 60, 332–340.
Effects of genetic and pharmacological inhibition of TNF-alpha in the regulation of inflammation in macrophages.Crossref | GoogleScholarGoogle Scholar | 19450684PubMed |

Dinarello, C. A. (2005). Blocking IL-1 in systemic inflammation. J. Exp. Med. 201, 1355–1359.
Blocking IL-1 in systemic inflammation.Crossref | GoogleScholarGoogle Scholar | 15867089PubMed |

Dong, J., Qu, Y., Li, J., Cui, L., Wang, Y., Lin, J., and Wang, H. (2018). Cortisol inhibits NF-κB and MAPK pathways in LPS activated bovine endometrial epithelial cells. Int. Immunopharmacol. 56, 71–77.
Cortisol inhibits NF-κB and MAPK pathways in LPS activated bovine endometrial epithelial cells.Crossref | GoogleScholarGoogle Scholar | 29367089PubMed |

Fabbri, M. (2012). TLRs as miRNA receptors. Cancer Res. 72, 6333–6337.
TLRs as miRNA receptors.Crossref | GoogleScholarGoogle Scholar | 23222301PubMed |

Flammini, L., Mantelli, L., Volpe, A., Domenichini, G., Di Lecce, R., Dondi, M., and Quintavalla, F. (2018). Rifaximin anti-inflammatory activity on bovine endometrium primary cell cultures: a preliminary study. Vet. Med. Sci. 4, 326–332.
Rifaximin anti-inflammatory activity on bovine endometrium primary cell cultures: a preliminary study.Crossref | GoogleScholarGoogle Scholar | 29984902PubMed |

Franke, W. W., Appelhans, B., Schmid, E., Freudenstein, C., Osborn, M., and Weber, K. (1979). Identification and characterization of epithelial cells in mammalian tissues by immunofluorescence microscopy using antibodies to prekeratin. Differentiation 15, 7–25.
Identification and characterization of epithelial cells in mammalian tissues by immunofluorescence microscopy using antibodies to prekeratin.Crossref | GoogleScholarGoogle Scholar |

Franke, W. W., Schiller, D. L., Moll, R., Winter, S., Schmid, E., Engelbrecht, I., and Platzer, B. (1981). Diversity of cytokeratins: differentiation specific expression of cytokeratin polypeptides in epithelial cells and tissues. J. Mol. Biol. 153, 933–959.
Diversity of cytokeratins: differentiation specific expression of cytokeratin polypeptides in epithelial cells and tissues.Crossref | GoogleScholarGoogle Scholar | 6177862PubMed |

Fumuso, E., Giguere, S., Wade, J., Rogan, D., Videla-Dorna, I., and Bowden, R. A. (2003). Endometrial IL-1beta, IL-6 and TNF-alpha, mRNA expression in mares resistant or susceptible to post-breeding endometritis. Effects of estrous cycle, artificial insemination and immunomodulation. Vet. Immunol. Immunopathol. 96, 31–41.
Endometrial IL-1beta, IL-6 and TNF-alpha, mRNA expression in mares resistant or susceptible to post-breeding endometritis. Effects of estrous cycle, artificial insemination and immunomodulation.Crossref | GoogleScholarGoogle Scholar | 14522132PubMed |

Gilbert, R. O., Shin, S. T., Guard, C. L., Erb, H. N., and Frajblat, M. (2005). Prevalence of endometritis and its effects on reproductive performance of dairy cows. Theriogenology 64, 1879–1888.
Prevalence of endometritis and its effects on reproductive performance of dairy cows.Crossref | GoogleScholarGoogle Scholar | 15961149PubMed |

Guan, J. Y., Liao, T. T., Yu, C. L., Luo, H. Y., Yang, W. R., and Wang, X. Z. (2018). ERK1/2 regulates heat stress-induced lactate production via enhancing the expression of HSP70 in immature boar Sertoli cells. Cell Stress Chaperones 23, 1193–1204.
ERK1/2 regulates heat stress-induced lactate production via enhancing the expression of HSP70 in immature boar Sertoli cells.Crossref | GoogleScholarGoogle Scholar | 29943101PubMed |

Healy, L. L., Cronin, J. G., and Sheldon, I. M. (2014). Endometrial cells sense and react to tissue damage during infection of the bovine endometrium via interleukin 1. Sci. Rep. 4, 7060.
Endometrial cells sense and react to tissue damage during infection of the bovine endometrium via interleukin 1.Crossref | GoogleScholarGoogle Scholar | 25395028PubMed |

Herath, S., Fischer, D. P., Werling, D., Williams, E. J., Lilly, S. T., Dobson, H., Bryant, C. E., and Sheldon, I. M. (2006). Expression and function of Toll-like receptor 4 in bovine endometrium. Endocrinology 147, 562–570.
Expression and function of Toll-like receptor 4 in bovine endometrium.Crossref | GoogleScholarGoogle Scholar | 16223858PubMed |

Hessam, S., Sand, M., Skrygan, M., Gambichler, T., and Bechara, F. (2017). Expression of miRNA-155, miRNA-223, miRNA-31, miRNA-21, miRNA-125b, and miRNA-146a in the inflammatory pathway of hidradenitis suppurativa. Inflammation 40, 464–472.
Expression of miRNA-155, miRNA-223, miRNA-31, miRNA-21, miRNA-125b, and miRNA-146a in the inflammatory pathway of hidradenitis suppurativa.Crossref | GoogleScholarGoogle Scholar | 28028756PubMed |

Hoffmann, A., Levchenko, A., Scott, M. L., and Baltimore, D. (2002). The IkappaB-NF-kappaB signaling module: temporal control and selective gene activation. Science 298, 1241–1245.
The IkappaB-NF-kappaB signaling module: temporal control and selective gene activation.Crossref | GoogleScholarGoogle Scholar | 12424381PubMed |

Huang, B., Xiao, D., Tan, B., Xiao, H., Wang, J., Yin, J., and Yin, Y. (2016). Chitosan oligosaccharide reduces intestinal inflammation that involves calcium-sensing receptor (CaSR) activation in lipopolysaccharide (LPS)-challenged piglets. J. Agric. Food Chem. 64, 245–252.
Chitosan oligosaccharide reduces intestinal inflammation that involves calcium-sensing receptor (CaSR) activation in lipopolysaccharide (LPS)-challenged piglets.Crossref | GoogleScholarGoogle Scholar | 26654156PubMed |

Jana, B., Jaroszewski, J. J., Czarzasta, J., and Markiewicz, W. (2015). The influence of leukotrienes C4 and D4 on the contractility of an inflamed porcine uterus. Theriogenology 83, 1328–1337.
The influence of leukotrienes C4 and D4 on the contractility of an inflamed porcine uterus.Crossref | GoogleScholarGoogle Scholar | 25707327PubMed |

Karin, M., Yamamoto, Y., and Wang, Q. M. (2004). The IKK NF-kappa B system: a treasure trove for drug development. Nat. Rev. Drug Discov. 3, 17–26.
The IKK NF-kappa B system: a treasure trove for drug development.Crossref | GoogleScholarGoogle Scholar | 14708018PubMed |

Kawai, T., and Akira, S. (2010). The role of pattern-recognition receptors in innate immunity: update on Toll-like receptors. Nat. Immunol. 11, 373–384.
The role of pattern-recognition receptors in innate immunity: update on Toll-like receptors.Crossref | GoogleScholarGoogle Scholar | 20404851PubMed |

Lan, T., Kisseleva, T., and Brenner, D. A. (2015). Deficiency of NOX1 or NOX4 prevents liver inflammation and fibrosis in mice through inhibition of hepatic stellate cell activation. PLoS One 10, e0129743.
Deficiency of NOX1 or NOX4 prevents liver inflammation and fibrosis in mice through inhibition of hepatic stellate cell activation.Crossref | GoogleScholarGoogle Scholar | 26709926PubMed |

Li, X., Shahid, M. Q., Wu, J. W., Wang, L., Liu, X. D., and Lu, Y. G. (2016). Comparative small RNA analysis of pollen development in autotetraploid and diploid rice. Int. J. Mol. Sci. 17, 499.
Comparative small RNA analysis of pollen development in autotetraploid and diploid rice.Crossref | GoogleScholarGoogle Scholar | 27077850PubMed |

Lim, J. Y., Hwang, B. Y., Hwang, K. W., and Park, S. Y. (2012). Methylalpinumisoflavone inhibits lipopolysaccharide-induced inflammation in microglial cells by the NF-kappaB and MAPK signaling pathway. Phytother. Res. 26, 1948–1956.
Methylalpinumisoflavone inhibits lipopolysaccharide-induced inflammation in microglial cells by the NF-kappaB and MAPK signaling pathway.Crossref | GoogleScholarGoogle Scholar | 22899404PubMed |

MacKintosh, S. B., Schuberth, H. J., Healy, L. L., and Sheldon, I. M. (2013). Polarised bovine endometrial epithelial cells vectorially secrete prostaglandins and chemotactic factors under physiological and pathological conditions. Reproduction 145, 57–72.
Polarised bovine endometrial epithelial cells vectorially secrete prostaglandins and chemotactic factors under physiological and pathological conditions.Crossref | GoogleScholarGoogle Scholar | 23115348PubMed |

Miwa, K., Asano, M., Horai, R., Iwakura, Y., Nagata, S., and Suda, T. (1998). Caspase 1-independent IL-1beta release and inflammation induced by the apoptosis inducer Fas ligand. Nat. Med. 4, 1287–1292.
Caspase 1-independent IL-1beta release and inflammation induced by the apoptosis inducer Fas ligand.Crossref | GoogleScholarGoogle Scholar | 9809553PubMed |

Moll, R., Franke, W. W., Schiller, D. L., Geiger, B., and Krepler, R. (1982). The catalog of human cytokeratins: patterns of expression in normal epithelia, tumors and cultured cells. Cell 31, 11–24.
The catalog of human cytokeratins: patterns of expression in normal epithelia, tumors and cultured cells.Crossref | GoogleScholarGoogle Scholar | 6186379PubMed |

Nahid, M. A., Satoh, M., and Chan, E. K. (2011). MicroRNA in TLR signaling and endotoxin tolerance. Cell. Mol. Immunol. 8, 388–403.
MicroRNA in TLR signaling and endotoxin tolerance.Crossref | GoogleScholarGoogle Scholar | 21822296PubMed |

Osuchowski, M. F., and Remick, D. G. (2006). The repetitive use of samples to measure multiple cytokines: the sequential ELISA. Methods 38, 304–311.
The repetitive use of samples to measure multiple cytokines: the sequential ELISA.Crossref | GoogleScholarGoogle Scholar | 16503163PubMed |

Perwez Hussain, S., and Harris, C. C. (2007). Inflammation and cancer: an ancient link with novel potentials. Int. J. Cancer 121, 2373–2380.
Inflammation and cancer: an ancient link with novel potentials.Crossref | GoogleScholarGoogle Scholar |

Pierce, J. W., Schoenleber, R., Jesmok, G., Best, J., Moore, S. A., Collins, T., and Gerritsen, M. E. (1997). Novel inhibitors of cytokine-induced IkappaBalpha phosphorylation and endothelial cell adhesion molecule expression show anti-inflammatory effects in vivo. J. Biol. Chem. 272, 21096–21103.
Novel inhibitors of cytokine-induced IkappaBalpha phosphorylation and endothelial cell adhesion molecule expression show anti-inflammatory effects in vivo.Crossref | GoogleScholarGoogle Scholar | 9261113PubMed |

Qi, J., Qiao, Y., Wang, P., Li, S., Zhao, W., and Gao, C. (2012). microRNA-210 negatively regulates LPS-induced production of proinflammatory cytokines by targeting NF-κB1 in murine macrophages. FEBS Lett. 586, 1201–1207.
microRNA-210 negatively regulates LPS-induced production of proinflammatory cytokines by targeting NF-κB1 in murine macrophages.Crossref | GoogleScholarGoogle Scholar | 22575656PubMed |

Qureshi, O. S., Bon, H., Twomey, B., Holdsworth, G., Ford, K., Bergin, M., and Hurdowar, V. (2017). An immunofluorescence assay for extracellular matrix components highlights the role of epithelial cells in producing a stable, fibrillar extracellular matrix. Biol. Open 6, 1423–1433.
An immunofluorescence assay for extracellular matrix components highlights the role of epithelial cells in producing a stable, fibrillar extracellular matrix.Crossref | GoogleScholarGoogle Scholar | 29032370PubMed |

Recchiuti, A., Krishnamoorthy, S., Fredman, G., Chiang, N., and Serhan, C. N. (2011). MicroRNAs in resolution of acute inflammation: identification of novel resolvin D1-miRNA circuits. FASEB J. 25, 544–560.
MicroRNAs in resolution of acute inflammation: identification of novel resolvin D1-miRNA circuits.Crossref | GoogleScholarGoogle Scholar | 20956612PubMed |

Rossomando, A. J., Payne, D. M., Weber, M. J., and Sturgill, T. W. (1989). Evidence that pp42, a major tyrosine kinase target protein, is a mitogen-activated serine/threonine protein kinase. Proc. Natl. Acad. Sci. USA 86, 6940–6943.
Evidence that pp42, a major tyrosine kinase target protein, is a mitogen-activated serine/threonine protein kinase.Crossref | GoogleScholarGoogle Scholar | 2550926PubMed |

Salilew-Wondim, D., Ibrahim, S., Gebremedhn, S., Tesfaye, D., Heppelmann, M., Bollwein, H., and Schellander, K. (2016). Clinical and subclinical endometritis induced alterations in bovine endometrial transcriptome and miRNome profile. BMC Genomics 17, 218.
Clinical and subclinical endometritis induced alterations in bovine endometrial transcriptome and miRNome profile.Crossref | GoogleScholarGoogle Scholar | 26965375PubMed |

Shen, C. L., Hong, K. J., and Kim, S. W. (2005). Comparative effects of ginger root (Zingiber officinale Rosc.) on the production of inflammatory mediators in normal and osteoarthritic sow chondrocytes. J. Med. Food 8, 149–153.
Comparative effects of ginger root (Zingiber officinale Rosc.) on the production of inflammatory mediators in normal and osteoarthritic sow chondrocytes.Crossref | GoogleScholarGoogle Scholar | 16117605PubMed |

Siemieniuch, M. J., Szóstek, A. Z., Gajos, K., Kozdrowski, R., Nowak, M., and Okuda, K. (2016). Type of inflammation differentially affects expression of interleukin 1β and 6, tumor necrosis factor-α and Toll-like receptors in subclinical endometritis in mares. PLoS One 11, e0154934.
Type of inflammation differentially affects expression of interleukin 1β and 6, tumor necrosis factor-α and Toll-like receptors in subclinical endometritis in mares.Crossref | GoogleScholarGoogle Scholar | 27152525PubMed |

Singh, R. P., Massachi, I., Manickavel, S., Singh, S., Rao, N. P., Hasan, S., and Hahn, B. H. (2013). The role of miRNA in inflammation and autoimmunity. Autoimmun. Rev. 12, 1160–1165.
The role of miRNA in inflammation and autoimmunity.Crossref | GoogleScholarGoogle Scholar | 23860189PubMed |

Smith, M. P., Sanchezlaorden, B., O’Brien, K., Brunton, H., Ferguson, J., Young, H., and Cooper, Z. A. (2014). The immune microenvironment confers resistance to MAPK pathway inhibitors through macrophage-derived TNFα. Cancer Discov. 4, 1214–1229.
The immune microenvironment confers resistance to MAPK pathway inhibitors through macrophage-derived TNFα.Crossref | GoogleScholarGoogle Scholar | 25256614PubMed |

Sun, B., Dwivedi, N., Bechtel, T. J., Paulsen, J. L., Muth, A., Bawadekar, M., and Schiffer, C. A. (2017). Citrullination of NF-κB p65 promotes its nuclear localization and TLR-induced expression of IL-1β and TNFα. Sci. Immunol. 2, eaal3062.
Citrullination of NF-κB p65 promotes its nuclear localization and TLR-induced expression of IL-1β and TNFα.Crossref | GoogleScholarGoogle Scholar | 28783661PubMed |

Theuß, T., Böttcher, D., Kappe, A., Schoon, H. A., and Ellenberger, C. (2010). Establishment of a new method for isolation and culture of equine endometrial epithelial and stromal cells. Pferdeheilkunde 26, 63–69.
Establishment of a new method for isolation and culture of equine endometrial epithelial and stromal cells.Crossref | GoogleScholarGoogle Scholar |

Tripathi, A., Paliwal, P., and Krishnamurthy, S. (2017). Piracetam attenuates LPS-induced neuro inflammation and cognitive impairment in rats. Cell. Mol. Neurobiol. 37, 1373–1386.
Piracetam attenuates LPS-induced neuro inflammation and cognitive impairment in rats.Crossref | GoogleScholarGoogle Scholar | 28176051PubMed |

Vera, L., Boyen, F., De, V. A., Vandenbroucke, V., Vanantwerpen, G., and Govaere, J. (2019). Limitations of a chromogenic agar plate for the identifying bacteria isolated from equine endometritis samples. Equine Vet. J. 51, 266–269.
Limitations of a chromogenic agar plate for the identifying bacteria isolated from equine endometritis samples.Crossref | GoogleScholarGoogle Scholar | 30080274PubMed |

Wei, W., Dejie, L., Xiaojing, S., Tiancheng, W., Yongguo, C., Zhengtao, Y., and Naisheng, Z. (2015). Magnolol inhibits the inflammatory response in mouse mammary epithelial cells and a mouse mastitis model. Inflammation 38, 16–26.
Magnolol inhibits the inflammatory response in mouse mammary epithelial cells and a mouse mastitis model.Crossref | GoogleScholarGoogle Scholar | 25173887PubMed |

Yang, J. W., Tian, G., Chen, D. W., Yao, Y., He, J., Zheng, P., and Yu, B. (2018). Involvement of PKA signalling in anti-inflammatory effects of chitosan oligosaccharides in IPEC-J2 porcine epithelial cells. J. Anim. Physiol. Anim. Nutr. (Berl.) 102, 252–259.
Involvement of PKA signalling in anti-inflammatory effects of chitosan oligosaccharides in IPEC-J2 porcine epithelial cells.Crossref | GoogleScholarGoogle Scholar |

Ye, F., Tang, C., Shi, W., Qian, J., Xiao, S., Gu, M., Dang, Y., Liu, J., Chen, Y., Shi, R., and Zhang, G. (2015). A MDM2-dependent positive-feedback loop is involved in inhibition of miR-375 and miR-106b induced by Helicobacter pylori lipopolysaccharide. Int. J. Cancer 136, 2120–2131.
A MDM2-dependent positive-feedback loop is involved in inhibition of miR-375 and miR-106b induced by Helicobacter pylori lipopolysaccharide.Crossref | GoogleScholarGoogle Scholar | 25307786PubMed |

Yu, C. L., Guan, J. Y., Ding, J., Huang, S., Lian, Y., Luo, H. Y., and Wang, X. Z. (2018). AMP-activated protein kinase negatively regulates heat treatment-induced lactate secretion in cultured boar Sertoli cells. Theriogenology 121, 35–41.
AMP-activated protein kinase negatively regulates heat treatment-induced lactate secretion in cultured boar Sertoli cells.Crossref | GoogleScholarGoogle Scholar | 30125826PubMed |

Young, M. D., Wakefield, M. J., Smyth, G. K., and Oshlack, A. (2010). Gene ontology analysis for RNA-seq: accounting for selection bias. Genome Biol. 11, R14.
Gene ontology analysis for RNA-seq: accounting for selection bias.Crossref | GoogleScholarGoogle Scholar | 20132535PubMed |

Zamore, P. D., and Haley, B. (2005). The big world of small RNAs. Science 309, 1519–1524.
The big world of small RNAs.Crossref | GoogleScholarGoogle Scholar | 16141061PubMed |

Zhai, W. J., Zhang, Z. B., Xu, N. N., Guo, Y. F., Qiu, C., Li, C. Y., and Guo, M. Y. (2016). Piperine plays an anti-inflammatory role in Staphylococcus aureus endometritis by inhibiting activation of NF-κB and MAPK pathways in mice. Evid. Based Complement. Alternat. Med. 2016, 8597208.
Piperine plays an anti-inflammatory role in Staphylococcus aureus endometritis by inhibiting activation of NF-κB and MAPK pathways in mice.Crossref | GoogleScholarGoogle Scholar | 27293467PubMed |

Zhang, H., Wang, Z., Fu, X., Sun, Y., Mi, Z., Yu, G., and Zhao, Q. (2018). A pathway-based association analysis identified FMNL1–MAP3K14 as susceptibility genes for leprosy. Exp. Dermatol. 27, 245–250.
A pathway-based association analysis identified FMNL1–MAP3K14 as susceptibility genes for leprosy.Crossref | GoogleScholarGoogle Scholar | 29283461PubMed |

Zhao, G., Jiang, K., Yang, Y., Zhang, T., Wu, H., Shaukat, A., and Deng, G. (2018). The potential therapeutic role of miR-223 in bovine endometritis by targeting the NLRP3 inflammasome. Front. Immunol. 9, 1916.
The potential therapeutic role of miR-223 in bovine endometritis by targeting the NLRP3 inflammasome.Crossref | GoogleScholarGoogle Scholar | 30186287PubMed |

Zhou, M., Yi, Y., and Hong, L. (2019). Oridonin ameliorates lipopolysaccharide-induced endometritis in mice via inhibition of the TLR-4/NF-κB pathway. Inflammation 42, 81–90.
Oridonin ameliorates lipopolysaccharide-induced endometritis in mice via inhibition of the TLR-4/NF-κB pathway.Crossref | GoogleScholarGoogle Scholar | 30132202PubMed |