Adenosine A3 Receptor Mediates ERK1/2- and JNK-Dependent TNF-α Production in Toxoplasma gondii-Infected HTR8/SVneo Human Extravillous Trophoblast Cells

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.

Medienart:

E-Artikel

Erscheinungsjahr:

2020

Erschienen:

2020

Enthalten in:

Zur Gesamtaufnahme - volume:58

Enthalten in:

The Korean journal of parasitology - 58(2020), 4 vom: 20. Aug., Seite 393-402

Sprache:

Englisch

Beteiligte Personen:

Ye, Wei [VerfasserIn]
Sun, Jinhui [VerfasserIn]
Li, Chunchao [VerfasserIn]
Fan, Xuanyan [VerfasserIn]
Gong, Fan [VerfasserIn]
Huang, Xinqia [VerfasserIn]
Deng, Mingzhu [VerfasserIn]
Chu, Jia-Qi [VerfasserIn]

Links:

Volltext

Themen:

ADORA3 protein, human
Adenosine A3 receptor
EC 2.7.11.24
EC 2.7.12.2
HTR8/SVneo trophoblast cell
Journal Article
MAP Kinase Kinase 4
MAPK
MAPK1 protein, human
MAPK3 protein, human
Mitogen-Activated Protein Kinase 1
Mitogen-Activated Protein Kinase 3
Receptor, Adenosine A3
TNF-α
Toxoplasma gondii
Tumor Necrosis Factor-alpha

Anmerkungen:

Date Completed 14.09.2020

Date Revised 14.09.2020

published: Print-Electronic

Citation Status MEDLINE

doi:

10.3347/kjp.2020.58.4.393

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM314446303