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Hydroxysafflor Yellow A Inhibits Staphylococcus aureus-Induced Mouse Endometrial Inflammation via TLR2-Mediated NF-kB and MAPK Pathway

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Abstract

The present study is designed to investigate the effect of hydroxysafflor yellow A (HYA) on Staphylococcus aureus (S. aureus)-induced mouse endometrial inflammation and to explore its molecular mechanism. We established a mouse endometritis model by intrauterine injection of S. aureus and intrauterine injection of HYA for treatment. Immunohistochemistry, immunofluorescence, and Western blot were used to detect protein expression in uterine tissue, and qPCR was used to measure mRNA expression. HYA could significantly weak uterine pathological changes caused by S. aureus and reduce MPO activity, CD45, CD3, and ED-1 protein expression in uterine tissues of S. aureus-infected mice. Similarly, HYA also significantly decreased S. aureus induced the increase in TNF-α, IL-1β, and IL-6 in uterine tissue. In vivo, we found that knockdown of TLR2 was very important could significantly reduce S. aureus induced the elevated expression of TNF-α, IL-1β, and IL-6 in mEECs. Importantly, in terine tissues of S. aureus-infected mice, HYA significantly decreased the ratio of p-p65/p65, p-IKBα/IKBα, p-p38/p38, p-Erk/Erk, and p-JNK/JNK expression. HYA displays anti-inflammatory effects on S. aureus mouse endometrial inflammation, and this effect might be related to HYA which could block TLR2-mediated NF-kB and MAPK pathway.

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References

  1. Woodward, E.M., and M.H.T. Troedsson. Inflammatory mechanisms of endometritis. Equine Veterinary Journal 47 (4): 384–389.

  2. Kitaya, Kotaro, Takumi Takeuchi, Shimpei Mizuta, Hidehiko Matsubayashi, and Tomomoto Ishikawa. 2018. Endometritis: New time, new concepts. Fertility and Sterility 110 (3): 344–350.

    Article  Google Scholar 

  3. Kushnir, Vitaly A., Shirley Solouki, Tal Sarig-Meth, Mario G. Vega, David F. Albertini, Sarah K. Darmon, Liane Deligdisch, David H. Barad, and Norbert Gleicher. 2016. Systemic inflammation and autoimmunity in women with chronic endometritis. American Journal of Reproductive Immunology 75 (6): 672–677.

    Article  CAS  Google Scholar 

  4. Sergio, Mella M. 2006. Daptomicina en infecciones invasoras por Staphylococcus aureus. The New England Journal of Medicine 23 (4): 653–665.

    Google Scholar 

  5. Tumminello, Antonio, Dennis Dominguez, Lebowitz Dan, Placido Bartolone, and Ilker Uçkay. 2017. Staphylococcus aureus versus streptococci in orthopaedic infections. Infectious Diseases 49 (9): 1.

    Article  Google Scholar 

  6. Kobayashi, Scott D., Natalia Malachowa, and Frank R. DeLeo. Pathogenesis of Staphylococcus aureus abscesses. American Journal of Pathology 185 (6): 1518–1527.

  7. Kobayashi, Scott D., Natalia Malachowa, and Frank R. Deleo. 2015. Infectious disease theme issue: Pathogenesis of Staphylococcus aureus abscesses. American Journal of Pathology 185 (6): 1518–1527.

    Article  Google Scholar 

  8. Smit, Jesper, Luis Eduardo López-Cortés, Reimar W. Thomsen, Henrik C. Schønheyder, and Mette Søgaard. 2017. Statin use and risk of community-acquired Staphylococcus aureus bacteremia. European Journal of Endocrinology 92 (10): 1469–1478.

    CAS  Google Scholar 

  9. Lam, John C., Daniel B. Gregson, Stephen Robinson, Ranjani Somayaji, and Michael D. Parkins. 2019. Epidemiology and outcome determinants of Staphylococcus aureus bacteremia revisited: A population-based study. Infection. 47: 961–971.

    Article  Google Scholar 

  10. Fetsch, A., M. Contzen, K. Hartelt, A. Kleiser, S. Maassen, J. Rau, B. Kraushaar, F. Layer, and B. Strommenger. Staphylococcus aureus food-poisoning outbreak associated with the consumption of ice-cream. International Journal of Food Microbiology 187: 1–6.

  11. Bastos, Caroline Peixoto, Milena Tomasi Bassani, Marcia Magalhães Mata, Graciela Volz Lopes, and Wladimir Padilha da Silva. 2017. Prevalence and expression of staphylococcal enterotoxin genes in Staphylococcus aureus isolated from food poisoning outbreaks. Canadian Journal of Microbiology 63 (10): 834–840.

    Article  CAS  Google Scholar 

  12. Zadoks, R.N., H.G. Allore, H.W. Barkema, O.C. Sampimon, and Y.H. Schukken. 2002. Cow- and quarter-level risk factors for Streptococcus uberis and Staphylococcus aureus mastitis. Journal of Dairy Science 84 (12).

  13. Hodille, Elisabeth, Warren Rose, Binh An Diep, Sylvain Goutelle, and Oana Dumitrescu. 2017. The role of antibiotics in modulating virulence in Staphylococcus aureus. Clinical Microbiology Reviews 30 (4): 887–917.

    Article  CAS  Google Scholar 

  14. Chambers, Henry F., and Frank R. DeLeo. Waves of resistance: Staphylococcus aureus in the antibiotic era. Nature Reviews Microbiology 7 (9): 629–641.

  15. Mcgaw, L.J., R. Gehring, L. Katsoulis, and J.N. Eloff. 2010. Is the use of Gunnera perpensa extracts in endometritis related to antibacterial activ. Onderstepoort Journal of Veterinary Research 72 (2): 129.

    Google Scholar 

  16. Wu, Haichong, Dai Ailing, Chen Xingxing, Xiaoyan Yang, Li Xiaohua, Huang Cuiqin, Jiang Kangfeng, and Ganzhen Deng. Leonurine ameliorates the inflammatory responses in lipopolysaccharide-induced endometritis. International Immunopharmacology 61: 156–161.

  17. Wu, Haichong, Jiang Kangfeng, Yin Nannan, Xiaofei Ma, Zhao Gan, Qiu Changwei, and Ganzhen Deng. Thymol mitigates lipopolysaccharide-induced endometritis by regulating the TLR4- and ROS-mediated NF-κB signaling pathways. Oncotarget 8 (12).

  18. Bonsale, R., R. Seyed Sharifi, E. Dirandeh, N. Hedayat, A. Mojtahedin, M. Ghorbanalinia, and A. Abolghasemi. Endocannabinoids as endometrial inflammatory markers in lactating Holstein cows. Reproduction in Domestic Animals.

  19. Xu, Xiaolong, Yuhong Guo, Zhao Jingxia, Ning Wang, Ding Junying, and Liu Qingquan. 2016. Hydroxysafflor yellow A inhibits LPS-induced NLRP3 inflammasome activation via binding to xanthine oxidase in mouse RAW264.7 macrophages. Mediators of Inflammation: 1–11.

  20. Li, Jie, Shenyang Zhang, Mengru Lu, Zhibin Chen, Cong Chen, Lijuan Han, Meijuan Zhang, and Yun Xu. Hydroxysafflor yellow A suppresses inflammatory responses of BV2 microglia after oxygen–glucose deprivation. Neuroscience Letters 535 (Complete): 51–56.

  21. Hu, X., J. Guo, M. Xu, P. Jiang, X. Yuan, C. Zhao, T. Maimai, Y. Cao, N. Zhang, and Y. Fu. 2019. Clostridium tyrobutyricum alleviates Staphylococcus aureus-induced endometritis in mice by inhibiting endometrial barrier disruption and inflammatory response. Food & Function 10 (10): 6699–6710. https://doi.org/10.1039/c9fo00654k.

    Article  CAS  Google Scholar 

  22. Zhang, Z., Y. Guo, Y. Liu, C. Li, M. Guo, and G. Deng. 2017. IFN-τ displays anti-inflammatory effects on Staphylococcus aureus Endometritis via inhibiting the activation of the NF-κB and MAPK pathways in mice. BioMed Research International 2017: 2350482–2350412. https://doi.org/10.1155/2017/2350482.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Liu, Y.L., Y.J. Liu, Y. Liu, X.S. Li, S.H. Liu, Y.G. Pan, J. Zhang, Q. Liu, and Y.Y. Hao. 2014. Hydroxysafflor yellow A ameliorates lipopolysaccharide-induced acute lung injury in mice via modulating toll-like receptor 4 signaling pathways. International Immunopharmacology 23 (2): 649–657. https://doi.org/10.1016/j.intimp.2014.10.018.

    Article  CAS  PubMed  Google Scholar 

  24. Wu, Y., L. Wang, M. Jin, and B.X. Zang. 2012. Hydroxysafflor yellow A alleviates early inflammatory response of bleomycin-induced mice lung injury. Biological & Pharmaceutical Bulletin 35 (4): 515–522. https://doi.org/10.1248/bpb.35.515.

    Article  Google Scholar 

  25. Herath, S., S.T. Lilly, N.R. Santos, R.O. Gilbert, L. Goetze, C.E. Bryant, J.O. White, J. Cronin, and I.M. Sheldon. 2009. Expression of genes associated with immunity in the endometrium of cattle with disparate postpartum uterine disease and fertility. Reproductive Biology and Endocrinology 7: 55. https://doi.org/10.1186/1477-7827-7-55.

    Article  CAS  PubMed  Google Scholar 

  26. Lv, Y., Y. Qian, L. Fu, X. Chen, H. Zhong, and X. Wei. 2015. Hydroxysafflor yellow A exerts neuroprotective effects in cerebral ischemia reperfusion-injured mice by suppressing the innate immune TLR4-inducing pathway. European Journal of Pharmacology 769: 324–332. https://doi.org/10.1016/j.ejphar.2015.11.036.

    Article  CAS  PubMed  Google Scholar 

  27. Takeda, K., T. Kaisho, and S. Akira. 2003. Toll-like receptors. Annual Review of Immunology 21: 335–376. https://doi.org/10.1146/annurev.immunol.21.120601.141126.

    Article  CAS  PubMed  Google Scholar 

  28. He, Yanhao, Qiang Liu, Yanxiang Li, Xiaofeng Yang, Weirong Wang, Tingting Li, Wei Zhang, Yuexin Cui, Chaoyun Wang, and Rong Lin. 2015. Protective effects of hydroxysafflor yellow A (HSYA) on alcohol-induced liver injury in rats. Journal of Physiology and Biochemistry 71 (1): 69–78.

    Article  CAS  Google Scholar 

  29. Serhan, Charles N., Nan Chiang, and Thomas E. Van Dyke. 2008. Resolving inflammation: Dual anti-inflammatory and pro-resolution lipid mediators. Nature Reviews Immunology 8 (5): 349–361.

    Article  CAS  Google Scholar 

  30. Barton, Gregory M., and Ruslan Medzhitov. 2003. Toll-like receptor signaling pathways. Science 300 (5625): 1524–1525.

    Article  CAS  Google Scholar 

  31. Kawai, Taro, and Shizuo Akira. 2006. TLR signaling. Cell Death & Differentiation 13 (5): 816–825.

    Article  CAS  Google Scholar 

  32. Negishi, Hideo, Yasuyuki Fujita, Hideyuki Yanai, Shinya Sakaguchi, Xinshou Ouyang, Masahiro Shinohara, Hiroshi Takayanagi, Yusuke Ohba, Tadatsugu Taniguchi, and Kenya Honda. 2006. Evidence for licensing of IFN-γ-induced IFN regulatory factor 1 transcription factor by MyD88 in Toll-like receptor-dependent gene induction program. 103 (41): 15136–15141.

  33. Muzio, and M. IRAK (Pelle). Family member IRAK-2 and MyD88 as proximal mediators of IL-1 signaling. Science 278 (5343): 1612–1615.

  34. Hirata, Y., T. Ohmae, W. Shibata, S. Maeda, K. Ogura, H. Yoshida, T. Kawabe, and M. Omata. MyD88 and TNF receptor-associated factor 6 are critical signal transducers in Helicobacter pylori-infected human epithelial cells. Journal of Immunology 176 (6): 3796–3803.

  35. Zhang, Guolong, and Sankar Ghosh. 2001. Toll-like receptor–mediated NF-κB activation: A phylogenetically conserved paradigm in innate immunity. The Journal of Clinical Investigation 107 (1): 13–19.

    Article  CAS  Google Scholar 

  36. Vasselon, Thierry, William A. Hanlon, Samuel D. Wright, and Patricia A. Detmers. 2002. Toll-like receptor 2 (TLR2) mediates activation of stress-activated MAP kinase p38. Journal of Leukocyte Biology 71 (3): 503–510.

    CAS  PubMed  Google Scholar 

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Author notes

  1. Shunzhi He, Xinrong Wang and Zhenteng Liu contributed equally to this work.

Authors and Affiliations

  1. Department of Reproductive Medicine, Yantai Yuhuangding Hospital, Qingdao University, 20, Yuhuangding East Road, Yantai City, 264000, Shandong Province, China

    Shunzhi He, Xinrong Wang, Zhenteng Liu, Wei Zhang, Jianye Fang, Jingwen Xue & Hongchu Bao

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  1. Shunzhi He
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  2. Xinrong Wang
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Correspondence to Hongchu Bao.

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He, S., Wang, X., Liu, Z. et al. Hydroxysafflor Yellow A Inhibits Staphylococcus aureus-Induced Mouse Endometrial Inflammation via TLR2-Mediated NF-kB and MAPK Pathway. Inflammation 44, 835–845 (2021). https://doi.org/10.1007/s10753-020-01297-8

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