EXPLORING EFFECTS OF INTERLEUKIN-33 ON JAK/STAT SIGNALLING PATHWAYS IN MACROPHAGES

Yıl 2022, Cilt: 4 Sayı: 1, 32 - 44, 30.04.2022

Mehmet Zafer Kalayci , Zubeyir Elmazoglu , Vedat Bulut

Öz

It is known that IL-33 cytokine plays role in pathogenesis of some diseases. The dual role of
macrophages within the tumor microenvironment is well-known and dependent on their plasticity.
Macrophages mainly serve as the component of innate immune system, but they also act as a bridge
between innate and acquired immune system with their antigen presentation capacity. Macrophages
can change their functions by being polarized to classical M1 and alternative M2 macrophages via
cytokine cocktails, such as interferon-, transforming growth factor- and interleukin-4, -10, -13. Tumor promoting effects are mainly associated with tumor-associated macrophages (TAMs)
resembling the M2 types of macrophages. On the other hand, macrophages shifted to M1 type are
capable of antitumour activities.
Investigation of down-stream intracellular signaling pathways is very important in order to
understand completely its role in pathogenesis of diseases mentioned above, as well as, to determine
appropriate hypothesis in studies of therapeutic agents related to down-stream intracellular signaling
pathways.
This study is aimed to enlighten the effect of IL-33 on tyrosine kinase and JAK/STAT intracellular
signaling pathways in macrophage cell line, J774.1. Therefore, mrIL-33 in several concentrations
will be added into cell cultures of J774 stimulated by IFN-γ plus LPS or unstimulated. Then, tyrosine
kinase (Tk) activities, levels and activation of Jak/STAT activities will be measured.
In this study, it was observed that IL-33 additions in prior to mrIFN-γ 40 U/mL plus LPS 10 ng/mL
stimulation decreased Tyk-2 levels in the group in which IL-33 levels were used at 10 ng/mL
(p<0.05). In order to monitor the effects of IL-33 on tyk2, it was observed that tyrosine kinase tyk2
levels did not change when IL-33 was added to cell cultures at 10ng/mL and 100 ng/mL
concentrations after 0, 4 and 18 hours. When IL-33 was applied to the J774.1 macrophage cell line at
a concentration of 10 ng/mL at different times, an increase in Tyk-2 phosphorylation was observed.
When IL-33 was applied to J774.1 cells at concentrations of 10 ng/mL and 100 ng/mL 4 and 18
hours before IFN-γ stimulation, statistically increased phosphorylated STAT levels were found in all
IL-33 applied groups compared to the control group. These results show that high-dose IL-33
administration creates a synergistic effect on STAT activation with IFN-γ stimulation.
This study will lead to observation of the effect of IL-33 in intracellular signaling pathways of
macrophages. Then, it will be going through the proper channels to understand effective mechanisms
of IL-33, as a therapeutic target in neoplasms.

Anahtar Kelimeler

IL-33, intracellular signaling pathways, tyrosine kinase, JAK, STAT, INF-γ

Kaynakça

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