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

Abstract

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