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Interleukin 6 is the classical member of the IL-6 family of cytokines which triggers activation of the JAK/STAT signaling cascade in cells. IL-6 is a pleiotropic cytokine that acts on many cell types and plays a critical role in immune responses, inflammation, and haematopoiesis. Our understanding of the molecular mechanisms governing IL-6 signaling has been aided by numerous studies of this signal transduction pathway, including those utilising the M1 cell line. Here we discuss the studies that we and others have undertaken using the M1 line to examine IL-6 inducible genes, particularly those targets that acts as negative regulators of signaling. Finally, we present a model for the current understanding of the IL-6 signaling pathway at a structural and mechanistic level., (Copyright © 2021. Published by Elsevier Ltd.)

Based on the complex crystal structure of human interleukin-6 (hIL-6) and its receptor (hIL-6R), a novel hIL-6 antagonist peptide (named PT) was designed using computer-guided design method. Dealing with molecular docking and molecular dynamics methods, the interaction between PT and hIL-6R was analyzed. The theoretical studies showed that PT possessed very high affinity to hIL-6R and offered a practical means of imposing long-term blockade of hIL-6 activity in vivo. This effect was examined due to growth arrest and apoptosis induced by hIL-6 in myeloblastic cell line M1 cells in a dose-dependent manner. The findings demonstrate that PT could also act as an excellent antagonist candidate for the induction of growth arrest and apoptosis. Furthermore, murine M1 myeloid cell line, which was induced by the physiological inducer hIL-6 to undergo apoptosis and growth arrest, could be used as a subtle model system to test hIL-6 antagonist. [Copyright &y& Elsevier]