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Jeg‐3 Human Choriocarcinoma‐Induced Immunosuppression: Downregulation of Interleukin‐2, Interleukin‐2 Receptor α‐Chain, and Its Jak/Stat Signaling Pathway
Author(s) -
Kilic M.,
Flossmann E.,
Flossmann O.,
Vogelsang H.,
Junker U.,
Chaouat G.,
Markert U.R.
Publication year - 1999
Publication title -
american journal of reproductive immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.071
H-Index - 97
eISSN - 1600-0897
pISSN - 1046-7408
DOI - 10.1111/j.1600-0897.1999.tb00076.x
Subject(s) - stat5 , janus kinase , signal transduction , stat1 , stat3 , microbiology and biotechnology , janus kinase 1 , cytokine , stat4 , biology , janus kinase 3 , chemistry , il 2 receptor , immunology , t cell , stat , immune system
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.