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What do you know about the three signaling pathways of IL-6?
IL-6 Overview:
In 1986, IL-6 was identified as a B cell stimulating factor that promotes the differentiation of effector B cells into antibody producing cells. IL-6, also known as IFN- β 2. Hepatocyte stimulating factor and hybridoma/plasma cell tumor growth factor are a 25 kDa secreted glycopeptide composed of 184 amino acids. Monocytes and macrophages are the main producers of IL-6. T cells, B cells, liver cells, endothelial cells, fibroblasts, keratinocytes, mesangial cells, adipocytes, and several types of tumor cells can also be formed or stimulated. IL-6 is a pleiotropic cytokine that can affect various immune and physiological processes, such as acute phase protein production, inflammation, antigen-specific immune response, hematopoiesis, cell apoptosis, differentiation, and cell metabolism.
IL-6R, gp130, sIL-6R and Three Signal Transductions
1. Classic signal transduction
In the classic signal cascade, only transmembrane 80-kDa is expressed α Cells with receptor subunit IL-6R (mIL-6R, CD126) respond to IL-6. Monomer complexes of IL-6 and mIL-6R with universally expressed 130 kDa β The receptor subunit receptors (gp130, CD130) bind and cause gp130 dimerization. Gp130 is a binding and signal transduction molecule of several members of the IL-6 family (oncostatin M, IL-11, CNRF-1, IL-27, IL 35).
2. Trans signal transduction
The soluble form of sIL-6R can form complexes with IL-6 and gp130. There are two ways to generate sIL-6R:
① Cutting mIL-6R through ADAM10/17
② By replacing RNA splicing
Soluble form of gp130 (sgp130), produced by alternative splicing. SIL-6R not only binds to its ligand IL-6, but also the IL-6 and sIL-6R complex can bind and activate gp130 on cells that do not carry membrane bound IL-6R. This process is called IL-6 trans signaling, which enhances the IL-6 target cell spectrum, explaining the pleiotropic function of IL-6.
3. Reverse presentation
After the interaction between dendritic cells (DCs) and antigens, IL-6, which has already been bound to IL-6R cells in DCs, is trans-represented to the plasma membrane. Then, the membrane binding IL-6/mIL-6R complex on DC interacts with gp130 on T cells, causing Th17 cells to interact with TGF- β Combined with IL-27, it induces the production of pathological Th17 cells, chronic inflammation, and inhibits Treg cells. This discovery originated from an experimental autoimmune encephalomyelitis mouse model (a mouse model used for human multiple sclerosis research), and still needs to be confirmed in humans.
For more experimental information, please consult our sales representative. Shanghai Hengyuan Biotechnology Co., Ltd. has its own laboratory and a professional technical research and development team. It has been committed to the research and sales of various biological reagents, cells, serum, and ELISA kits for a long time. We provide free testing services for experiments and exquisite technical services. If you have any questions about experiments, please feel free to come and consult us, and we will provide you with professional one-on-one technical guidance.
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