Dimethyl itaconate protects against lipopolysaccharide-induced endometritis by inhibition of TLR4/NF-κB and activation of Nrf2/HO-1 signaling pathway in mice

被引:21
作者
Xu, Mingyue [1 ]
Jiang, Peng [1 ]
Sun, Haowen [1 ]
Yuan, Xin [1 ]
Gao, Siyuan [1 ]
Guo, Jian [1 ]
Zhao, Caijun [1 ]
Hu, Xiaoyu [1 ]
Liu, Xueshibojie [2 ]
Fu, Yunhe [1 ]
机构
[1] Jilin Univ, Coll Vet Med, Dept Clin Vet Med, Changchun 130062, Jilin, Peoples R China
[2] Jilin Univ, Affiliated Hosp 2, Dept Otolaryngol Head & Neck Surg, Changchun, Peoples R China
基金
中国国家自然科学基金;
关键词
Dimethyl itaconate; Endometritis; LPS; NF-kappa B; Nrf2; TLR4; NF-KAPPA-B; OXIDATIVE STRESS; SUCCINATE-DEHYDROGENASE; INFLAMMATION; METABOLITE; NRF2;
D O I
10.22038/ijbms.2020.44151.10346
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
Objective(s): Endometritis is the inflammation of the uterine lining that is associated with infertility. It affects milk production and reproductive performance and leads to huge economic losses in dairy cows. Dimethyl itaconate (DI), a promising chemical agent, has recently been proved to have multiple health-promoting effects. However, the effects of DI on endometritis remain to be unknown. Materials and Methods: In this study, we assessed the anti-inflammatory effects of DI on Lipopolysaccharide (LPS)-induced endometritis in mice. The endometritis was induced by LPS treatment for 24 hr, and DI was given 24 hr before induction of LPS. Results: As a result, DI administered mice significantly suffered less impairment of uterine tissue and less recruitment of inflammatory cells than LPS administered mice. In addition, DI markedly inhibited uterine myeloperoxidase (MPO) activity and pro-inflammatory cytokines of tumor necrosis factor alpha (TNF-alpha) and interleukin 6 (IL-6) induced by LPS. Moreover, LPS-induced toll-like receptor 4/nuclear factor-kappa B (TLR4/NF-kappa B) activation was suppressed by DI. In addition, the expressions of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase (HO-1) were upregulated by DI. Conclusion: These findings suggest that DI has anti-inflammatory functions in the LPS-induced mice and may be a therapeutic agent against endometritis.
引用
收藏
页码:1239 / 1244
页数:6
相关论文
共 35 条
[1]   I-KAPPA-B - A SPECIFIC INHIBITOR OF THE NF-KAPPA-B TRANSCRIPTION FACTOR [J].
BAEUERLE, PA ;
BALTIMORE, D .
SCIENCE, 1988, 242 (4878) :540-546
[2]   Electrophilic properties of itaconate and derivatives regulate the IκBζ-ATF3 inflammatory axis [J].
Bambouskova, Monika ;
Gorvel, Laurent ;
Lampropoulou, Vicky ;
Sergushichev, Alexey ;
Loginicheva, Ekaterina ;
Johnson, Kendall ;
Korenfeld, Daniel ;
Mathyer, Mary Elizabeth ;
Kim, Hyeryun ;
Huang, Li-Hao ;
Duncan, Dustin ;
Bregman, Howard ;
Keskin, Abdurrahman ;
Santeford, Andrea ;
Apte, Rajendra S. ;
Sehgal, Raghav ;
Johnson, Britney ;
Amarasinghe, Gaya K. ;
Soares, Miguel P. ;
Satoh, Takashi ;
Akira, Shizuo ;
Hai, Tsonwin ;
Strong, Cristina de Guzman ;
Auclair, Karine ;
Roddy, Thomas P. ;
Biller, Scott A. ;
Jovanovic, Marko ;
Klechevsky, Eynav ;
Stewart, Kelly M. ;
Randolph, Gwendalyn J. ;
Artyomov, Maxim N. .
NATURE, 2018, 556 (7702) :501-+
[3]   Pro-inflammatory cytokine expression studies of subclinical and clinical endometritis in endometrial tissues of buffaloes [J].
Bhadaniya, A. R. ;
Prasad, M. C. ;
Saysani, H. ;
Kalaria, V. A. ;
Fefar, D. T. ;
Mathpati, S. ;
Javia, B. B. .
TROPICAL ANIMAL HEALTH AND PRODUCTION, 2019, 51 (05) :1161-1166
[4]   Itaconate charges down inflammation [J].
Bordon, Yvonne .
NATURE REVIEWS IMMUNOLOGY, 2018, 18 (06) :360-361
[5]   Immunoresponsive Gene 1 and Itaconate Inhibit Succinate Dehydrogenase to Modulate Intracellular Succinate Levels [J].
Cordes, Thekla ;
Wallace, Martina ;
Michelucci, Alessandro ;
Divakaruni, Ajit S. ;
Sapcariu, Sean C. ;
Sousa, Carole ;
Koseki, Haruhiko ;
Cabrales, Pedro ;
Murphy, Anne N. ;
Hiller, Karsten ;
Metallo, Christian M. .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2016, 291 (27) :14274-14284
[6]   Berberine hydrochloride attenuates lipopolysaccharide-induced endometritis in mice by suppressing activation of NF-κB signal pathway [J].
Fu, Kaiqiang ;
Lv, Xiaopei ;
Li, Weishi ;
Wang, Yu ;
Li, Huatao ;
Tian, Wenru ;
Cao, Rongfeng .
INTERNATIONAL IMMUNOPHARMACOLOGY, 2015, 24 (01) :128-132
[7]   New regulators of NF-κB in inflammation [J].
Ghosh, Sankar ;
Hayden, Matthew S. .
NATURE REVIEWS IMMUNOLOGY, 2008, 8 (11) :837-848
[8]   LPS induction of gene expression in human monocytes [J].
Guha, M ;
Mackman, N .
CELLULAR SIGNALLING, 2001, 13 (02) :85-94
[9]   Small Molecule Restores Itaconate Sensitivity in Salmonella enterica: A Potential New Approach to Treating Bacterial Infections [J].
Hammerer, Fabien ;
Chang, Justin H. ;
Duncan, Dustin ;
Ruiz, Angel Castaneda ;
Auclair, Karine .
CHEMBIOCHEM, 2016, 17 (16) :1513-1517
[10]   Nrf2-regulated glutathione recycling independent of biosynthesis is critical for cell survival during oxidative stress [J].
Harvey, C. J. ;
Thimmulappa, R. K. ;
Singh, A. ;
Blake, D. J. ;
Ling, G. ;
Wakabayashi, N. ;
Fujii, J. ;
Myers, A. ;
Biswal, S. .
FREE RADICAL BIOLOGY AND MEDICINE, 2009, 46 (04) :443-453