Review Article

The Many Faces of Interleukin-6: The Role of IL-6 in Inflammation, Vasculopathy, and Fibrosis in Systemic Sclerosis

Figure 1

Interleukin-6 trans signalling. IL-6 receptors are expressed on leukocytes including neutrophils, but they are not expressed on tissue-resident cells, for example, endothelial cells. Endothelial cells can respond to IL-6 through the gp130 receptor only when the IL-6 is bound to a soluble IL-6 receptor (sIL-6R). sIL-6Rs are formed by secretion of an alternatively spliced version of the receptor or proteolytic cleavage from the surface of neutrophils. There is also a pool of soluble gp130 (sgp130) which can bind IL-6/sIL6R complexes and prevent them binding to cellular gp130. Therefore, the local concentrations of IL-6, sIL-6R, and sgp130 regulate IL-6 signalling.
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