Biochimica et Biophysica Acta (BBA) - Molecular Cell Research
ReviewThe pro- and anti-inflammatory properties of the cytokine interleukin-6
Graphical abstract
Legend:
Cells that express both gp130 and the membrane bound IL-6R are responsive to IL-6 (classic signaling). In contrast, cells that express gp130 but not IL-6R can only be activated by the complex of IL-6 and soluble IL-6R (sIL-6R). Activation of cells by the IL-6/sIL-6R complex is termed trans-signaling. The sIL-6R is generated by proteolytic cleavage of the membrane bound precursor by membrane bound metalloproteases of the ADAM family. The sIL-6R binds IL-6 with comparable affinity as the membrane bound form and mediates gp130 activation in an (1) autocrine or (2) paracrine manner.
Research Highlights
► The cytokine interleukin-6 (IL-6) has pro- and anti-inflammatory properties. ► Whereas only few cells express the IL-6 receptor and respond to IL-6 (classic signaling), all cells can be stimulated via a soluble IL-6 receptor (trans-signaling) since gp130 is ubiquitously expressed. ► Classic- and trans-signaling can be differentially inhibited. ► Apparently, IL-6 via classic signaling has regenerative and anti-inflammatory functions whereas trans-signaling is pro-inflammatory.