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. 2016 Sep 21;6:34012. doi: 10.1038/srep34012

Figure 6. Model for the regulation of IL-6 production by NE in SSc fibroblasts.

Figure 6

Emotional stress and/or cold exposure might increase systemic and/or local NE levels. Production of IL-6 in SSc fibroblasts was enhanced by both NE and ARβ agonist, isoproterenol, but not ARα agonist, oxymetazoline, suggesting that NE-induced IL-6 production is primarily mediated via ARβ. NE binds to and activates the downstream signaling of ARβ, thus leading to the phosphorylation of p38. This NE-induced activation of p38 signaling may consequently enhance IL-6 production in SSc fibroblasts. In contrast, the NE-induced phosphorylation of ERK1/2 via ARα subsequently results in the inhibition of IL-6 production in SSc fibroblasts. NE-induced IL-6 production and proliferation of fibroblasts might lead to skin fibrosis in SSc. ET: endothelin. ETR: endothelin receptor.