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Regulation of S100As Expression by Inflammatory Cytokines in Chronic Lymphocytic Leukemia

Institute for Medical Research, National Institute of Republic of Serbia, University of Belgrade, 11129 Belgrade, Serbia
Lymphoma Center, Clinic for Hematology, University Clinical Center of Serbia, 11000 Belgrade, Serbia
Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2022, 23(13), 6952;
Received: 16 May 2022 / Revised: 18 June 2022 / Accepted: 20 June 2022 / Published: 22 June 2022
(This article belongs to the Section Molecular Oncology)
The calcium-binding proteins S100A4, S100A8, and S100A9 are upregulated in chronic lymphocytic leukemia (CLL), while the S100A9 promotes NF-κB activity during disease progression. The S100-protein family has been involved in several malignancies as mediators of inflammation and proliferation. The hypothesis of our study is that S100A proteins are mediators in signaling pathways associated with inflammation-induced proliferation, such as NF-κB, PI3K/AKT, and JAK/STAT. The mononuclear cells (MNCs) of CLL were treated with proinflammatory IL-6, anti-inflammatory IL-10 cytokines, inhibitors of JAK1/2, NF-κB, and PI3K signaling pathways, to evaluate S100A4, S100A8, S100A9, and S100A12 expression as well as NF-κB activation by qRT-PCR, immunocytochemistry, and immunoblotting. The quantity of S100A4, S100A8, and S100A9 positive cells (p < 0.05) and their protein expression (p < 0.01) were significantly decreased in MNCs of CLL patients compared to healthy controls. The S100A levels were generally increased in CD19+ cells compared to MNCs of CLL. The S100A4 gene expression was significantly stimulated (p < 0.05) by the inhibition of the PI3K/AKT signaling pathway in MNCs. IL-6 stimulated S100A4 and S100A8 protein expression, prevented by the NF-κB and JAK1/2 inhibitors. In contrast, IL-10 reduced S100A8, S100A9, and S100A12 protein expressions in MNCs of CLL. Moreover, IL-10 inhibited activation of NF-κB signaling (4-fold, p < 0.05). In conclusion, inflammation stimulated the S100A protein expression mediated via the proliferation-related signaling and balanced by the cytokines in CLL. View Full-Text
Keywords: inflammation; IL-6; IL-10; CLL; prognostic markers inflammation; IL-6; IL-10; CLL; prognostic markers
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MDPI and ACS Style

Mitrović Ajtić, O.; Subotički, T.; Diklić, M.; Đikić, D.; Vukotić, M.; Dragojević, T.; Živković, E.; Antić, D.; Čokić, V. Regulation of S100As Expression by Inflammatory Cytokines in Chronic Lymphocytic Leukemia. Int. J. Mol. Sci. 2022, 23, 6952.

AMA Style

Mitrović Ajtić O, Subotički T, Diklić M, Đikić D, Vukotić M, Dragojević T, Živković E, Antić D, Čokić V. Regulation of S100As Expression by Inflammatory Cytokines in Chronic Lymphocytic Leukemia. International Journal of Molecular Sciences. 2022; 23(13):6952.

Chicago/Turabian Style

Mitrović Ajtić, Olivera, Tijana Subotički, Miloš Diklić, Dragoslava Đikić, Milica Vukotić, Teodora Dragojević, Emilija Živković, Darko Antić, and Vladan Čokić. 2022. "Regulation of S100As Expression by Inflammatory Cytokines in Chronic Lymphocytic Leukemia" International Journal of Molecular Sciences 23, no. 13: 6952.

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