Parasites, Hosts and Diseases

"TNF-α"

Original Articles

Adenosine A₃ Receptor Mediates ERK1/2- and JNK-Dependent TNF-α Production in Toxoplasma gondii-Infected HTR8/SVneo Human Extravillous Trophoblast Cells: Wei Ye, Jinhui Sun, Chunchao Li, Xuanyan Fan, Fan Gong, Xinqia Huang, Mingzhu Deng, Jia-Qi Chu; Korean J Parasitol 2020;58(4):393-402.
Published online August 25, 2020; DOI: https://doi.org/10.3347/kjp.2020.58.4.393

Abstract
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Toxoplasma gondii is an intracellular parasite that causes severe disease when the infection occurs during pregnancy. Adenosine is a purine nucleoside involved in numerous physiological processes; however, the role of adenosine receptors in T. gondii-induced trophoblast cell function has not been investigated until now. The goal of the present study was to evaluate the intracellular signaling pathways regulated by adenosine receptors using a HTR-8/SVneo trophoblast cell model of T. gondii infection. HTR8/SVneo human extravillous trophoblast cells were infected with or without T. gondii and then evaluated for cell morphology, intracellular proliferation of the parasite, adenosine receptor expression, TNF-α production and mitogen-activated protein (MAP) kinase signaling pathways triggered by adenosine A₃ receptor (A₃AR). HTR8/SVneo cells infected with T. gondii exhibited an altered cytoskeletal changes, an increased infection rate and reduced viability in an infection time-dependent manner. T. gondii significantly promoted increased TNF-α production, A₃AR protein levels and p38, ERK1/2 and JNK phosphorylation compared to those observed in uninfected control cells. Moreover, the inhibition of A₃AR by A₃AR siRNA transfection apparently suppressed the T. gondii infection-mediated upregulation of TNF-α, A₃AR production and MAPK activation. In addition, T. gondii-promoted TNF-α secretion was dramatically attenuated by pretreatment with PD098059 or SP600125. These results indicate that A₃AR-mediated activation of ERK1/2 and JNK positively regulates TNF-α secretion in T. gondii-infected HTR8/SVneo cells.

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LINC00152 knockdown exerts repressive effects on epithelial-mesenchymal transition in bladder cancer
Guoping Wang, Meijun Han, Fei Chen, Jinquan Liu, Jie Zhang
Cytotechnology.2025;[Epub] CrossRef
Structural Simplification from Tricyclic to Bicyclic Scaffolds: A Long-Term Investigation in the Field of Adenosine Receptor Antagonists
Costanza Ceni, Sara Calenda, Giulia Vagnoni, Daniela Catarzi, Flavia Varano, Vittoria Colotta
Cells.2025; 14(18): 1480. CrossRef
Suppression by central adenosine A3 receptors of the cholinergic defense against cardiovascular aberrations of sepsis: role of PI3K/MAPKs/NFκB signaling
Amany E. El-Naggar, Mai M. Helmy, Sahar M. El-Gowilly, Mahmoud M. El-Mas
Frontiers in Pharmacology.2024;[Epub] CrossRef
Modeling the human placental barrier to understand Toxoplasma gondii´s vertical transmission
Paula Faral-Tello, Romina Pagotto, Mariela Bollati-Fogolín, Maria E. Francia
Frontiers in Cellular and Infection Microbiology.2023;[Epub] CrossRef
TNF-α/anti-TNF-αdrugs and its effect on pregnancy outcomes
Fang-fang Dai, Min Hu, Yu-wei Zhang, Rong-hui Zhu, Li-ping Chen, Zhi-dian Li, Yan-jie Huang, Wei Hu, Yan-xiang Cheng
Expert Reviews in Molecular Medicine.2022;[Epub] CrossRef

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Involvement of PI3K/AKT and MAPK Pathways for TNF-α Production in SiHa Cervical Mucosal Epithelial Cells Infected with Trichomonas vaginalis: 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; Korean J Parasitol 2015;53(4):371-377.
Published online August 25, 2015; DOI: https://doi.org/10.3347/kjp.2015.53.4.371

Abstract
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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.

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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
Interactions between bacterial vaginosis-associated microbiota and Trichomonas vaginalis modulate parasite-induced pathogenicity and host immune responses
Shu-Fang Chiu, Ching-Yun Huang, Chien-Yung Chen, Wei-Jane Hsu, Yuan-Ming Yeh, Ya-Wen Shih, Lichieh Julie Chu, Wei-Ning Lin, Kuo-Yang Huang
Parasites & Vectors.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

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12 Web of Science
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Breast-Feeding Protects Infantile Diarrhea Caused by Intestinal Protozoan Infections: Ekhlas Hamed Abdel-Hafeez, Usama Salah Belal, Manal Zaki Mohamed Abdellatif, Koji Naoi, Kazumi Norose; Korean J Parasitol 2013;51(5):519-524.
Published online October 31, 2013; DOI: https://doi.org/10.3347/kjp.2013.51.5.519

Abstract
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This study investigated the effect of breast-feeding in protection against protozoan infection in infants with persistent diarrhea. Infants were classified into 2 groups; 161 breast-fed infants and the same number of non-breast-fed infants. Microscopic examinations of stool were done for detection of parasites and measuring the intensity of infection. Moreover, serum levels of IgE and TNF-α were measured by ELISA. Cryptosporidium spp., Entamoeba histolytica/Entamoeba dispar, Giardia lamblia, and Blastocystis sp. were demonstrated in infants with persistent diarrhea. The percentage of protozoan infections was significantly lower in breast-fed infants than that in the non-breast-fed infants. The levels of IgE and TNF-α were significantly lower in the breast-fed group than in the non-breast-fed group. There were significant positive associations between the serum levels of IgE and TNF-α and the intensity of parasite infection in the breast-fed group. It is suggested that breast-feeding has an attenuating effect on the rate and intensity of parasite infection.

Citations

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Selected Protective Mechanisms of Human Milk Against Intestinal Protozoal Infections in Infants
Joanna Wróblewska, Anna Długosz, Marcin Wróblewski, Jarosław Nuszkiewicz, Paweł Sutkowy, Alina Woźniak
Current Issues in Molecular Biology.2025; 47(8): 674. CrossRef
Giardia lamblia risk factors and burden in children with acute gastroenteritis in a Nicaraguan birth cohort
Lester Gutiérrez, Nadja A. Vielot, Roberto Herrera, Yaoska Reyes, Christian Toval-Ruíz, Patricia Blandón, Rebecca J. Rubinstein, Javier Mora, Luther A. Bartelt, Filemón Bucardo, Sylvia Becker-Dreps, Samuel Vilchez, Sarman Singh
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Tradeoffs in milk immunity affect infant infectious disease risk
Katherine Wander, Masako Fujita, Siobhan M Mattison, Margaret Duris, Megan Gauck, Tessa Hopt, Katherine Lacy, Angela Foligno, Rebecca Ulloa, Connor Dodge, Frida Mowo, Ireen Kiwelu, Blandina T Mmbaga
Evolution, Medicine, and Public Health.2022; 10(1): 295. CrossRef
Intestinal Parasitic Infections Among Pediatric Patients in a Metropolitan City of Bangladesh With Emphasis on Cryptosporidiosis
Nusrat Jahan Nipa, Nasima Aktar, Hasina M Hira, Farhana Akter, Dilshad Jahan, Salequl Islam, Ayukafangha Etando, Adnan Abdullah, Kona Chowdhury, Rahnuma Ahmad, Ahsanul Haq, Mainul Haque
Cureus.2022;[Epub] CrossRef
Association of genetic polymorphism at tumor necrosis factor-α gene promoter - 1031T/C and parasitic infections among children in Northern South Africa
N.C. Davhana, A.K. ElBakri, P.O. Bessong, A. Samie
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Antibodies, prophylaxis, transmission
Pierre Lutgen
Pharmacy & Pharmacology International Journal.2018;[Epub] CrossRef
Parasiticidal effect of synthetic bovine lactoferrin peptides on the enteric parasite Giardia intestinalis
Hugo Aguilar-Diaz, Adrian Canizalez-Roman, Tomas Nepomuceno-Mejia, Francisco Gallardo-Vera, Yolanda Hornelas-Orozco, Kamran Nazmi, Jan G.M. Bolscher, Julio Cesar Carrero, Claudia Leon-Sicairos, Nidia Leon-Sicairos
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Parasites & Vectors.2017;[Epub] CrossRef
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María A. Echevarría, María L. Eva
Current Tropical Medicine Reports.2017; 4(3): 178. CrossRef
Molecular Analysis of the Enteric Protozoa Associated with Acute Diarrhea in Hospitalized Children
Sonia Boughattas, Jerzy M. Behnke, Khalid Al-Ansari, Aarti Sharma, Wafa Abu-Alainin, Asma Al-Thani, Marawan A. Abu-Madi
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Killing of Cryptosporidium sporozoites by Lactoferrin
Jose Luis Paredes, Hayley Sparks, A. Clinton White Jr., Griselle Martinez-Traverso, Theresa Ochoa, Alejandro Castellanos-González
The American Journal of Tropical Medicine and Hygiene.2017; 97(3): 774. CrossRef
Role of Eosinophils and Tumor Necrosis Factor Alpha in Interleukin-25-Mediated Protection from Amebic Colitis
Zannatun Noor, Koji Watanabe, Mayuresh M. Abhyankar, Stacey L. Burgess, Erica L. Buonomo, Carrie A. Cowardin, William A. Petri, Alan Sher, Ralph Budd, Kris Chadee
mBio.2017;[Epub] CrossRef
Evolution of Socioeconomic Conditions and Its Relation to Spatial–Temporal Changes of Giardiasis and Helminthiasis in Amazonian Children
B. M. Delfino, R. G. Campos, T. M. Pereira, S. A. S. Mantovani, H. Oliart-Guzmán, A. C. Martins, A. M. Braña, F. L. C. C. Branco, J. A. Filgueira-Júnior, A. P. Santos, T. S. Araújo, C. S. M. Oliveira, A. A. Ramalho, P. T. Muniz, C. T. Codeço, M. da Silva-
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Alline R. Pacheco, Daniela Barile, Mark A. Underwood, David A. Mills
Annual Review of Animal Biosciences.2015; 3(1): 419. CrossRef
Exclusive breast feeding in early infancy reduces the risk of inpatient admission for diarrhea and suspected pneumonia in rural Vietnam: a prospective cohort study
Sarah Hanieh, Tran T. Ha, Julie A. Simpson, Tran T. Thuy, Nguyen C. Khuong, Dang D. Thoang, Thach D. Tran, Tran Tuan, Jane Fisher, Beverley-Ann Biggs
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Noninvasive intestinal amebiasis
Gayatri V. Nair, Easwaran P. Variyam
Current Opinion in Infectious Diseases.2014; 27(5): 465. CrossRef
Breastfeeding and risk of parasitic infection-a review
Prameela Kannan Kutty
Asian Pacific Journal of Tropical Biomedicine.2014; 4(11): 847. CrossRef

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Brief Communications

Increased Cytokine and Nitric Oxide Levels in Serum of Dogs Experimentally Infected with Rangelia vitalii: Francine C. Paim, Aleksandro S. Da Silva, Carlos Breno V. Paim, Raqueli T. Fran?a, M?rcio M. Costa, Marta M. M. F. Duarte, Manuela B. Sangoi, Rafael N. Moresco, Silvia G. Monteiro, Sonia Terezinha A. Lopes; Korean J Parasitol 2013;51(1):133-137.
Published online February 18, 2013; DOI: https://doi.org/10.3347/kjp.2013.51.1.133

Abstract
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This study aimed to measure the levels of interferon-gamma (IFN-γ), tumor necrosis factor-alpha (TNF-α), interleukin 1 (IL-1), interleukin 6 (IL-6), and nitrite/nitrate (NO_x) in serum of dogs experimentally infected with Rangelia vitalii. Twelve female mongrel dogs were divided into 2 groups; group A (uninfected controls) composed by healthy dogs (n=5) and group B consisting of dogs inoculated with R. vitalii (n=7). Animals were monitored by blood smear examinations, which showed intraerythrocytic forms of the parasite on day 5 post-infection (PI). Blood samples were collected through the jugular vein on days 0, 10, and 20 PI to determine the serum levels of IFN-γ, TNF-α, IL-1, IL-6, and NO_x. Cytokines were assessed by ELISA quantitative sandwich technique, and NO_x was measured by the modified Griess method. Cytokine levels (IFN-γ, TNF-α, IL-1, and IL-6) were increased (P<0.01) in serum of infected animals. Serum levels of NO_x were also increased on days 10 PI (P<0.01) and 20 PI (P<0.05) in infected animals. Therefore, the infection with R. vitalii causes an increase in proinflammatory cytokines and nitric oxide content. These alterations may be associated with host immune protection against the parasite.

Citations

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Immune and Genomic Analysis of Boxer Dog Breed and Its Relationship with Leishmania infantum Infection
Luis Álvarez, Pablo-Jesús Marín-García, Pilar Rentero-Garrido, Lola Llobat
Veterinary Sciences.2022; 9(11): 608. CrossRef
Disease severity and blood cytokine concentrations in dogs with natural Babesia rossi infection
Andrew Leisewitz, Amelia Goddard, Jill De Gier, Jessica Van Engelshoven, Sarah Clift, Peter Thompson, Johan P. Schoeman
Parasite Immunology.2019;[Epub] CrossRef
Cytokine Concentrations Measured by Multiplex Assays in Canine Peripheral Blood Samples
Kristen R. Richter, Amirah N. Nasr, Angela M. Mexas
Veterinary Pathology.2018; 55(1): 53. CrossRef
Relation of antioxidant status at admission and disease severity and outcome in dogs naturally infected with Babesia canis canis
Martina Crnogaj, José Joaquin Cerón, Iva Šmit, Ivana Kiš, Jelena Gotić, Mirna Brkljačić, Vesna Matijatko, Camila Peres Rubio, Nada Kučer, Vladimir Mrljak
BMC Veterinary Research.2017;[Epub] CrossRef
Serum biochemistry profile, inflammatory cytokines, adipokines and cardiovascular findings in obese dogs
Diego Piantedosi, Antonio Di Loria, Jacopo Guccione, Angela De Rosa, Silvia Fabbri, Laura Cortese, Sergio Carta, Paolo Ciaramella
The Veterinary Journal.2016; 216: 72. CrossRef
Excessive Pro-Inflammatory Serum Cytokine Concentrations in Virulent Canine Babesiosis
Amelia Goddard, Andrew L. Leisewitz, Mads Kjelgaard-Hansen, Annemarie T. Kristensen, Johan P. Schoeman, Michelle L. Baker
PLOS ONE.2016; 11(3): e0150113. CrossRef
Canine rangeliosis due to Rangelia vitalii: From first report in Brazil in 1910 to current day – A review
Raqueli T. França, Aleksandro S. Da Silva, Alexandre P. Loretti, Cinthia M. Mazzanti, Sonia T.A. Lopes
Ticks and Tick-borne Diseases.2014; 5(5): 466. CrossRef
Increased concentration of serum TNF alpha and its correlations with arterial blood pressure and indices of renal damage in dogs infected with Babesia canis
Wojciech Zygner, Olga Gójska-Zygner, Piotr Bąska, Ewa Długosz
Parasitology Research.2014; 113(4): 1499. CrossRef
Increase nitric oxide and oxidative stress in dogs experimentally infected by Ehrlichia canis: Effect on the pathogenesis of the disease
Aleksandro S. Da Silva, Thiago D. Munhoz, Joice L.M. Faria, Giovanni Vargas-Hérnandez, Rosangela Z. Machado, Taís C. Almeida, Rafael N. Moresco, Lenita M. Stefani, Mirela Tinucci-Costa
Veterinary Microbiology.2013; 164(3-4): 366. CrossRef

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Expression of TNF-α and IL-1β in Splenic Dendritic Cells and Their Serum Levels in Mouse Sparganosis: Hyun-Jong Yang; Korean J Parasitol 2011;49(2):191-194.
Published online June 14, 2011; DOI: https://doi.org/10.3347/kjp.2011.49.2.191

Abstract
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Sparganosis is a tissue invading helminthiasis infecting intermediate hosts, including humans. Strong immune responses are expected to occur in early phases of infection. Thus, we investigated cytokine expressions in splenic dendritic cells and in sera after experimental infection of mice. In splenic dendritic cells, TNF-α and IL-1β expression peaked at week 1 and week 3 post-infection (PI), respectively, and also early phase (week 2 PI) depressed cytokine expression was noticed. Serum IL-1β concentration increased significantly at week 2 PI and peaked at week 6 PI, and that of TNF-α peaked at week 6 PI. These results showed that pro-inflammatory cytokines, TNF-α and IL-1β, are chronologically regulated in mouse sparganosis.

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Original Article

Single Nucleotide Polymorphisms of Cytokine Genes are Associated with Fibrosis of the Intrahepatic Bile Duct Wall in Human Clonorchiasis: Byung-Suk Chung, Jeong-Keun Lee, Min-Ho Choi, Myoung Hee Park, Dongil Choi, Sung-Tae Hong; Korean J Parasitol 2009;47(2):145-151.
Published online May 27, 2009; DOI: https://doi.org/10.3347/kjp.2009.47.2.145

Abstract
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This study examined the association of cytokine gene polymorphisms with intrahepatic bile duct wall fibrosis in human clonorchiasis. A total of 240 residents in Heilongjiang, China underwent ultrasonography, blood sampling, and stool examination. Single nucleotide polymorphism (SNP) sites for IFN-γ (+874 T/A), IL-10 (-1,082 G/A, -819 C/T, -592 C/A), TNF-α (-308 G/A), and TGF-β1 (codon 10 T/C, codon 25 G/C) genes were observed with the TaqMan allelic discrimination assay. No significant correlation was observed between individual cytokine gene polymorphisms and intrahepatic duct dilatation (IHDD). Among individuals with clonorchiasis of moderate intensity, the incidence of IHDD was high in those with IFN-γ intermediate-producing genotype, +874AT (80.0%, P = 0.177), and in those with TNF-α low-producing genotype, -308GG (63.0%, P = 0.148). According to the combination of IFN-γ and TNF-α genotypes, the risks for IHDD could be stratified into high (intermediate-producing IFN-γ and low producing TNF-α), moderate, and low (low-producing IFN-γ and high producing TNF-α) risk groups. The incidence of IHDD was significantly different among these groups (P = 0.022): 88.9% (odds ratio, OR = 24.0) in high, 56.5% (OR = 3.9) in moderate, and 25.0% (OR = 1) in low risk groups. SNP of IFN-γ and TNF-α genes may contribute to the modulation of fibrosis in the intrahepatic bile duct wall in clonorchiasis patients.

Citations

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