HE2000 upregulates expression of the interferon gamma receptor in the L. donovani-infected U937 human macrophage cell line

• Published in: Journal of allergy and clinical immunology 2004-02, Vol.113 (2), p.S203-S203
• Main Authors: Carr, W.W., Hershey, J., Nelson, M.
• Format: Article
• Language: English
• ISSN: 0091-6749; 1097-6825
• DOI: 10.1016/j.jaci.2004.01.176

Since a Th2 bias is associated with L. donovoni infection, the causative agent of visceral leishmaniasis, we conducted a pilot study with a human macrophage cell line to determine if treatment with the immune modifying hormone HE2000 resulted in upregulation of the IFNγ receptor, indicating a shift to a protective Th1 response. With 6 treatment arms (2-7) and one parallel infection control arm (1), human macrophage U937 cells were cultured overnight in the presence of PMA prior to infection with L. donovani. Arms 1, 3, 4 and 6 were infected 24 hrs after PMA differentiation at a parasite to macrophage ratio of 10:1. Arms 2, 5, and 7 represent uninfected arms. Arms 2-7 were primed with IFNγ and arms 2,4,5 and 6 were treated with HE2000. Cells were examined by flow cytometry for the presence of the IFNγR-α chain. Arm 1 confirmed infection by Giemsa staining. Arms 3 (infected) and 7 (uninfected) did not receive HE2000 and yielded 13.1% and 12.3% expression of the IFNγR-α chain, respectively. Expression rate for arm 2 (uninfected + HE2000 1 day after IFNγ) was 14.1% and for arm 5 (uninfected + HE2000 & IFNγ at same time) 16.8%. IFNγR-α chain expression for arm 4 (infected + HE2000 & IFNγ at same time) was 23.1% and for arm 6 (infected + HE2000 1 day after IFNγ) 52.7%. Treatment of L. donovani infected U937 human macrophage cells with HE2000 results in upregulation of the IFNγR-α chain. No upregulation occurs in uninfected HE2000-treated cells.