IL-19 and Other IL-20 Family Member Cytokines in Vascular Inflammatory Diseases

Abstract

Cardiovascular disease remains a major medical and socioeconomic burden in developed and developing countries and will increase with an aging and increasingly sedentary society. Many vascular diseases and atherosclerotic vascular disease, in particular, are essentially inflammatory disorders, involving multiple cell types. Communication between these cells is initiated and sustained by a complex network of cytokines and their receptors. The interleukin (IL)-20 family members, IL-19, IL-20, IL-22, and IL-24, initiate, sustain, and drive the progression of vascular disease. They are important in vascular disease as they facilitate a bidirectional cross-talk between resident vascular cells with immune cells. These cytokines are grouped into the same family based on shared common receptor subunits and signaling pathways. This communication is varied and can result in exacerbation, attenuation, and even repair of the vasculature. We will briefly review what is known about IL-20, IL-22, and IL-24 in cardiovascular biology. Because IL-19 is the most studied member of this family in terms of its role in vascular pathophysiological processes, the major emphasis of this review will focus on the expression and atheroprotective roles of IL-19 in vascular inflammatory disease.

Keywords: atherosclerosis; interleukin-19; interleukin-20; restenosis; smooth muscle cell; vascular inflammation.

Figure 1

Illustration of interleukin (IL)-20 receptor system utilized by IL-19, IL-20, and IL-24. IL-20 receptor Type I is heterodimer composed of IL-20R1 and IL-20R2 and is recognized by IL-19, IL-20, and IL-24. IL-20 receptor Type II is a heterodimer composed of IL-20R2 and IL-22R and recognized only by IL-20 and IL-24. Each of these receptor complexes is capable of interacting with and activating a repertoire of JAK and STAT-signaling proteins. This multiplicity of ligand recognition and effector protein utilization offers combinational diversity in signal transduction and distal cellular processes. JAK, Janus Kinase; STAT, signal transducer and activator of transcription.

Figure 2

Interleukin-19 (IL-19) has direct and indirect vasculo-protective effects. IL-19 reduces VSMC inflammation and proliferation by reduction of HuR nucleocytoplasmic translocation and reduction of HuR protein abundance. HuR also protects VSMC by the induction of hemeoxygenase-1 expression. IL-19 polarizes T lymphocytes to the Th2 and macrophage to the M2 phenotype, each skewed toward anti-inflammatory and reparative characteristics. Together, this results in less pro-inflammatory and proliferative gene expression, resulting in reduced vascular inflammation. HO-1, Heme oxygenase-1, HuR, Human antigen R, VSMC, vascular smooth muscle cell.