Regulation of S100As Expression by Inflammatory Cytokines in Chronic Lymphocytic Leukemia
Аутори
Mitrović-Ajtić, OliveraSubotički, Tijana
Diklić, Miloš
Đikić, Dragoslava
Vukotić, Milica
Dragojević, Teodora
Živković, Emilija
Antić, Darko
Čokić, Vladan
Чланак у часопису (Објављена верзија)
Метаподаци
Приказ свих података о документуАпстракт
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 gener...ally 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.
Кључне речи:
inflammation / IL-6 / IL-10 / CLL / prognostic markersИзвор:
International Journal of Molecular Sciences, 2022, 23, 13, 6952-Издавач:
- MDPI
Финансирање / пројекти:
- Министарство науке, технолошког развоја и иновација Републике Србије, институционално финансирање - 200015 (Универзитет у Београду, Институт за медицинска истраживања) (RS-MESTD-inst-2020-200015)
Институција/група
Institut za medicinska istraživanjaTY - JOUR AU - Mitrović-Ajtić, Olivera AU - Subotički, Tijana AU - Diklić, Miloš AU - Đikić, Dragoslava AU - Vukotić, Milica AU - Dragojević, Teodora AU - Živković, Emilija AU - Antić, Darko AU - Čokić, Vladan PY - 2022 UR - http://rimi.imi.bg.ac.rs/handle/123456789/1244 AB - 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. PB - MDPI T2 - International Journal of Molecular Sciences T1 - Regulation of S100As Expression by Inflammatory Cytokines in Chronic Lymphocytic Leukemia IS - 13 SP - 6952 VL - 23 DO - 10.3390/ijms23136952 ER -
@article{ author = "Mitrović-Ajtić, Olivera and Subotički, Tijana and Diklić, Miloš and Đikić, Dragoslava and Vukotić, Milica and Dragojević, Teodora and Živković, Emilija and Antić, Darko and Čokić, Vladan", year = "2022", abstract = "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.", publisher = "MDPI", journal = "International Journal of Molecular Sciences", title = "Regulation of S100As Expression by Inflammatory Cytokines in Chronic Lymphocytic Leukemia", number = "13", pages = "6952", volume = "23", doi = "10.3390/ijms23136952" }
Mitrović-Ajtić, O., Subotički, T., Diklić, M., Đikić, D., Vukotić, M., Dragojević, T., Živković, E., Antić, D.,& Čokić, V.. (2022). Regulation of S100As Expression by Inflammatory Cytokines in Chronic Lymphocytic Leukemia. in International Journal of Molecular Sciences MDPI., 23(13), 6952. https://doi.org/10.3390/ijms23136952
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. in International Journal of Molecular Sciences. 2022;23(13):6952. doi:10.3390/ijms23136952 .
Mitrović-Ajtić, Olivera, Subotički, Tijana, Diklić, Miloš, Đikić, Dragoslava, Vukotić, Milica, Dragojević, Teodora, Živković, Emilija, Antić, Darko, Čokić, Vladan, "Regulation of S100As Expression by Inflammatory Cytokines in Chronic Lymphocytic Leukemia" in International Journal of Molecular Sciences, 23, no. 13 (2022):6952, https://doi.org/10.3390/ijms23136952 . .