The anti‐inflammatory cytokine IL‐19 suppresses VSMC activation by attenuation of proliferative and inflammatory gene expression

Abstract

The development of multiple vascular diseases are inflammatory in nature. Interleukin‐19 (IL‐19) is a recently described member of the IL‐10 family of anti‐inflammatory cytokines. Nothing has been reported on the expression or mechanism(s) of IL‐19 effects in vascular cells. We have found that IL‐19 is not expressed in quiescent vascular smooth muscle cells (VSMC) or normal arteries, but is induced in VSMC by inflammatory cytokines and in arteries by injury. IL‐19 is anti‐proliferative for human coronary artery VSMC, and reduces inflammation‐stimulated expression of proliferative and inflammatory gene proteins, including Cyclins B and D, CDK, IL‐8, and COX2. IL‐19 transiently reduces expression of HuR, an inflammatory gene mRNA stabilizing transcription factor. Actinomycin D transcription blockade, and quantitative RT‐PCR assessment of mRNA shows that IL‐19 treatment reduced abundance of these mRNAs to 50–60% of untreated controls. (P<0.001 for all genes). IL‐19 inhibits serine phosphorylation of HuR, which is necessary for its cytoplasmic translocation. Since the mRNA stabilizing function of HuR is linked to its cytoplasmic translocation, this indicates that not only does IL‐19 decrease HuR accumulation, but also its activity. Together, these data indicate that one potential mechanism whereby IL‐19 inhibits VSMC proliferation and gene expression is by a reduction in expression and function of HuR.