Trichomonas vaginalis induces proinflammation in cervicovaginal mucosal epithelium. To investigate the signaling pathways in TNF-α production in cervical mucosal epithelium after T. vaginalis infection, the phosphorylation of PI3K/AKT and MAPK pathways were evaluated in T. vaginalis-infected SiHa cells in the presence and absence of specific inhibitors. T. vaginalis increased TNF-α production in SiHa cells, in a parasite burden-dependent and incubation time-dependent manner. In T. vaginalis-infected SiHa cells, AKT, ERK1/2, p38 MAPK, and JNK were phosphorylated from 1 hr after infection; however, the phosphorylation patterns were different from each other. After pretreatment with inhibitors of the PI3K/AKT and MAPK pathways, TNF-α production was significantly decreased compared to the control; however, TNF-α reduction patterns were different depending on the type of PI3K/MAPK inhibitors. TNF-α production was reduced in a dose-dependent manner by treatment with wortmannin and PD98059, whereas it was increased by SP600125. These data suggested that PI3K/AKT and MAPK signaling pathways are important in regulation of TNF-α production in cervical mucosal epithelial SiHa cells. However, activation patterns of each pathway were different from the types of PI3K/MAPK pathways.
Citations
Citations to this article as recorded by
Exploring the therapeutic potential and in vitro validation of baicalin for the treatment of triple-negative breast cancer Yuan Ma, Ying Pan, Qiancheng Zhao, Chongheng Zhang, Haitao He, Lihua Pan, Jianling Jia, Aiping Shi, Yiming Yang, Wenfeng Zhang Frontiers in Pharmacology.2025;[Epub] CrossRef
PI3K/AKT signaling in parasites and parasite diseases: Role and therapeutic potential Lujun Yan, Yating Li, Xing Yang, Rui Li, Chunyin Zhu, Xuedong He, Xiaoliang Jin, Guanghui Zheng, Naunain Mehmood, William C. Cho, Shijun Bao, Houhui Song, Yadong Zheng Virulence.2025;[Epub] CrossRef
Therapeutic effects of coptisine derivative EHLJ7 on colorectal cancer by inhibiting PI3K/AKT pathway ChangWei Chai, XiaoNan Tang, XiaoQian Chi, Xiang Li, HaiJing Zhang, LianQiu Wu Cellular Signalling.2024; 116: 111053. CrossRef
Inflammatory responses during trichomoniasis: The role of Toll‐like receptors and inflammasomes Abdollah Jafarzadeh, Maryam Nemati, Ehsan Salarkia, Sonal Yadav, Najmeh Aminizadeh, Sara Jafarzadeh, Manisha Yadav Parasite Immunology.2023;[Epub] CrossRef
Chemokine CXCL10 regulates pain behaviors via PI3K-AKT signaling pathway in mice Yan Fang, Xiaoling Peng, Huilian Bu, Xiaoqian Jia, Feng Gao, Cheng Liu Neuropeptides.2022; 93: 102243. CrossRef
The role of TNF-α induced protein 1 in the activation of pro-apoptotic proteins Xiaoren Tang, Thanarut Tangkham, Bushra Aljahdali, Sean Lee, Mingfang Su, Serge Dibart Human Cell.2021; 34(4): 1123. CrossRef
Prevention of EHLJ7 on Colitis-Associated Colorectal Cancer Tumorigenesis Through Regulating PI3K/AKT Pathway XiaoNan Tang, ChangWei Chai, Ying Guan, Xiang Li, AnJun Deng, HaiLin Qin, HaiJing Zhang, Lianqiu Wu SSRN Electronic Journal .2021;[Epub] CrossRef
LncRNA MNX1‐AS1 promotes the progression of cervical cancer through activating MAPK pathway Xiang Liu, Qian Yang, Jinyu Yan, Xiahui Zhang, Meiyun Zheng Journal of Cellular Biochemistry.2019; 120(3): 4268. CrossRef
Trichomonas vaginalis Induces Production of Proinflammatory Cytokines in Mouse Macrophages Through Activation of MAPK and NF-κB Pathways Partially Mediated by TLR2 Ling Li, Xin Li, Pengtao Gong, Xichen Zhang, Zhengtao Yang, Ju Yang, Jianhua Li Frontiers in Microbiology.2018;[Epub] CrossRef
Mapping out p38MAPK Elizabeth A. Bonney American Journal of Reproductive Immunology.2017;[Epub] CrossRef
C5a Induces the Synthesis of IL-6 and TNF-α in Rat Glomerular Mesangial Cells through MAPK Signaling Pathways Mingde Ji, Yanlai Lu, Chenhui Zhao, Wenxing Gao, Fengxia He, Jing Zhang, Dan Zhao, Wen Qiu, Yingwei Wang, Hiroyasu Nakano PLOS ONE.2016; 11(9): e0161867. CrossRef
Trichomonas vaginalis secretes a number of proteases which are suspected to be the cause of pathogenesis; however, little is understood how they manipulate host cells. The mammalian target of rapamycin (mTOR) regulates cell growth, cell proliferation, cell motility, cell survival, protein synthesis, and transcription. We detected various types of metalloproteinases including GP63 protein from T. vaginalis trophozoites, and T. vaginalis GP63 metalloproteinase was confirmed by sequencing and western blot. When SiHa cells were stimulated with live T. vaginalis, T. vaginalis excretory-secretory products (ESP) or T. vaginalis lysate, live T. vaginalis and T. vaginalis ESP induced the mTOR cleavage in both time- and parasite load-dependent manner, but T. vaginalis lysate did not. Pretreatment of T. vaginalis with a metalloproteinase inhibitor, 1,10-phenanthroline, completely disappeared the mTOR cleavage in SiHa cells. Collectively, T. vaginalis metallopeptidase induces host cell mTOR cleavage, which may be related to survival of the parasite.
Citations
Citations to this article as recorded by
Chromatin accessibility and gene expression in the parasite Trichomonas vaginalis Agustina Prat, Daniela Muñoz, Ayelen Lizarraga, Julieta Seifert-Gorzycki, Estefania Sanchez-Vazquez, Patricia J. Johnson, Pablo H. Strobl-Mazzulla, Natalia de Miguel BMC Infectious Diseases.2025;[Epub] CrossRef
Metallopeptidases as Key Virulence Attributes of Clinically Relevant
Protozoa: New Discoveries, Perspectives, and Frontiers of Knowledge Graziela Vargas Rigo, Fernanda Gomes Cardoso, Giulia Bongiorni Galego, Deisiane Fernanda da Rosa, André Luis Souza dos Santos, Tiana Tasca Current Protein & Peptide Science.2023; 24(4): 307. CrossRef
VPS32, a member of the ESCRT complex, modulates adherence to host cells in the parasite Trichomonas vaginalis by affecting biogenesis and cargo sorting of released extracellular vesicles Nehuén Salas, Veronica M. Coceres, Tuanne dos Santos Melo, Antonio Pereira-Neves, Vanina G. Maguire, Tania M. Rodriguez, Bruna Sabatke, Marcel I. Ramirez, Jihui Sha, James A. Wohlschlegel, Natalia de Miguel Cellular and Molecular Life Sciences.2022;[Epub] CrossRef
Adherent Bacteria and Parasiticidal Secretion Products of Human Cervicovaginal Microbiota-Associated Lactobacillus gasseri Confer Non-Identical Cell Protection against Trichomonas vaginalis-Induced Cell Detachment Bénédicte Pradines, Séverine Domenichini, Vanessa Lievin-Le Moal Pharmaceuticals.2022; 15(11): 1350. CrossRef
The 50 kDa metalloproteinase TvMP50 is a zinc-mediated Trichomonas vaginalis virulence factor Jonathan Puente-Rivera, José Luis Villalpando, Alma Villalobos-Osnaya, Laura Isabel Vázquez-Carrillo, Gloria León-Ávila, María Dolores Ponce-Regalado, César López-Camarillo, Jose Miguel Elizalde-Contreras, Eliel Ruiz-May, Rossana Arroyo, María Elizbeth Al Molecular and Biochemical Parasitology.2017; 217: 32. CrossRef
Regulation of exosomes released from normal ovarian epithelial cells and ovarian cancer cells Wei Zhang, Jiaxin Yang, Dongyan Cao, Yan You, Keng Shen, Peng Peng Tumor Biology.2016; 37(12): 15763. CrossRef
Involvement of PI3K/AKT and MAPK Pathways for TNF-α Production in SiHa Cervical Mucosal Epithelial Cells Infected with <i>Trichomonas vaginalis</i> Jung-Bo Yang, Juan-Hua Quan, Ye-Eun Kim, Yun-Ee Rhee, Byung-Hyun Kang, In-Wook Choi, Guang-Ho Cha, Jae-Min Yuk, Young-Ha Lee The Korean Journal of Parasitology.2015; 53(4): 371. CrossRef
First
Prev
