Jeg-3 Human Choriocarcinoma-Induced Immunosuppression: Downregulation of Interleukin-2, Interleukin-2 Receptor α-Chain, and Its Jak/Stat Signaling Pathway

Authors


Markert, Institut für Klinische Immunologie, Friedrich-Schiller-Universität, 07740 Jena, Germany.

Abstract

PROBLEM: The mechanisms of the immunosuppressive and immunosuppression-in-ducing capacities of Jeg-3 human choriocarcinoma cell line supernatants (HCSs) are not yet completely understood. The influence on interleukin (IL)-2, IL-4 and interferon (IFN)-γ production; IL-2 receptor (IL-2R) α-, β-, and γ-chain; and the signaling pathway molecules Janus kinase (Jak)1, Jak3, signal transducers and activators of transcription (Stat)1, Stat3, and Stat5 should be investigated.

METHOD OF STUDY: For assessment of IL production, whole peripheral venous blood from healthy donors was stimulated with phorbol-myristate-acetate and ionomycine. Secretion of ILs was blocked with monensine. Intracellular ILs were analyzed by flow cytometry. For IL-2R and signaling pathway molecule analysis, peripheral blood lymphocytes were stimulated with phytohemagglutinin (PHA). IL-2R chains were measured by flow cytometry, and Jaks/Stats by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and Western blot.

RESULTS: Phorbol-myristate-acetate and ionomycine strongly increase the percentage of IL-2+ cells; an additional 50% HCSs significantly suppresses the percentage to, or below the level of unstimulated cells. IFN-γ production is strongly decreased by HCSs in some cases, but not in others. PHA stimulates IL-2R α-, β-, and γ-chain expression and their signaling pathway molecules Jak1, Jak3, Stat1, Stat3, and Stat5. 50% HCS downregulates the α-chain and slightly upregulates the β-chain. Jak1, Jak3, Stat1, Stat3, and Stat5 expression is suppressed approximately to, or below the level of unstimulated cells.

CONCLUSIONS: HCS forcefully blocks the production of IL-2; the IL-2R α-chain; and Jak1, Jak3, Stat1, Stat3, and Stat5 expression. The observed phenomena might be caused by downregulation of an IL-2R regulation gene, and might play a key role in the expansion of choriocarcinoma, and possibly in the survival of the fetal allograft.

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