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. Author manuscript; available in PMC: 2019 Mar 16.
Published in final edited form as: Circ Genom Precis Med. 2019 Feb;12(2):e002413. doi: 10.1161/CIRCGEN.118.002413

Figure 6.

Figure 6

Overview of the IL-6 classical and trans-signalling pathways and their potential role in AAA growth. Notes: A - In “classical” IL-6 signalling (left), the binding of the cytokine IL-6 to the membrane-bound IL-6 receptor (mIL-6R) leads to the dimerization of its co-receptor gp130, and subsequently, triggers downstream signalling in a restricted subset of cells. In IL-6 trans-signalling (right), IL-6 forms a complex with soluble IL-6 receptor (sIL-6R) that can stimulate cells expressing gp130 even in the absence of mIL-6R. The minor allele of a functional variant in the IL6R gene, Asp358Ala (rs2228145 A>C) results in more efficient proteolytic cleavage of mIL-6R, thereby reducing levels of mIL-6R and classical IL-6 signalling but potentially increasing trans-signalling. B - In mouse models of AAA, the blockage of both the classical and trans-signalling pathways with anti-IL6-R (i.e. MR16-1, the animal-equivalent of tocilizumab) did not have a conclusive effect on the time to aneurysm rupture. C - Specific blockage of the trans-signalling pathway with sgp130 resulted in improved survival rates in mouse models of AAA.