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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-\u03b1 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-\u03b1 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-\u03b1, A3AR production and MAPK activation. In addition, T. gondii-promoted TNF-\u03b1 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-\u03b1 secretion in T. gondii-infected HTR8\/SVneo cells.<\/jats:p>","DOI":"10.3347\/kjp.2020.58.4.393","type":"journal-article","created":{"date-parts":[[2020,8,26]],"date-time":"2020-08-26T05:17:50Z","timestamp":1598419070000},"page":"393-402","update-policy":"https:\/\/doi.org\/10.3347\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Adenosine A3 Receptor Mediates ERK1\/2- and JNK-Dependent TNF-\u03b1 Production in Toxoplasma gondii-Infected HTR8\/SVneo Human Extravillous Trophoblast 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