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Int J Mol Sci. 2017 Dec 15;18(12). pii: E2715. doi: 10.3390/ijms18122715.

Femtograms of Interferon-γ Suffice to Modulate the Behavior of Jurkat Cells: A New Light in Immunomodulation.

Author information

1
Dipartimento di Scienze Biomediche e Cliniche L. Sacco, Università di Milano, I-20157 Milan, Italy. sara.castiglioni@unimi.it.
2
Clinical Research Unit, GUNA S.p.a., Via Palmanova, 71, 20132 Milan, Italy. v.miranda@guna.it.
3
Dipartimento di Scienze Biomediche e Cliniche L. Sacco, Università di Milano, I-20157 Milan, Italy. alessandra.cazzaniga@unimi.it.
4
Clinical Research Unit, GUNA S.p.a., Via Palmanova, 71, 20132 Milan, Italy. m.campanella@guna.it.
5
Service of Biostatistics Hematology Department Niguarda Ca' Granda Hospital, 20162 Milan, Italy. michele_nichelatti@hotmail.com.
6
Dipartimento di Scienze Biomediche e Cliniche L. Sacco, Università di Milano, I-20157 Milan, Italy. marcoandena@gmail.com.
7
Dipartimento di Scienze Biomediche e Cliniche L. Sacco, Università di Milano, I-20157 Milan, Italy. jeanette.maier@unimi.it.

Abstract

Since interferon-γ (IFN-γ) tunes both innate and adaptive immune systems, it was expected to enter clinical practice as an immunomodulatory drug. However, the use of IFN-γ has been limited by its dose-dependent side effects. Low-dose medicine, which is emerging as a novel strategy to treat diseases, might circumvent this restriction. Several clinical studies have proved the efficacy of therapies with a low dose of cytokines subjected to kinetic activation, while no in vitro data are available. To fill this gap, we investigated whether low concentrations, in the femtogram range, of kinetically activated IFN-γ modulate the behavior of Jurkat cells, a widely used experimental model that has importantly contributed to the present knowledge about T cell signaling. In parallel, IFN-γ in the nanogram range was used and shown to activate Signal transducer and activator of transcription (STAT)-1 and then to induce suppressor of cytokine signaling-1 (SOCS-1), which inhibits downstream signaling. When added together, femtograms of IFN-γ interfere with the transduction cascade activated by nanograms of IFN-γ by prolonging the activation of STAT-1 through the downregulation of SOCS-1. We conclude that femtograms of IFN-γ exert an immunomodulatory action in Jurkat cells.

KEYWORDS:

Jurkat cells; SOCS-1; STAT-1; immunomodulation; interferon-γ

PMID:
29244717
PMCID:
PMC5751316
DOI:
10.3390/ijms18122715
[Indexed for MEDLINE]
Free PMC Article

Conflict of interest statement

Sara Castiglioni, Alessandra Cazzaniga, Michele Nichelatti, Marco Andena and Jeanette A. M. Maier have no conflicting commercial or financial interests. Vincenzo Miranda and Marilena Campanella work for the pharmaceutical company GUNA S.p.a., Italy, which develops and commercializes immunological therapeutic products. This professional relationship does not, however, influence these authors’ scientific neutrality. Michele Nichelatti has worked and works as a consultant statistician for GUNA S.p.a. No products, patents, or other commercial interests relate to this study.

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