IL-10 up-regulates CCL5 expression in vascular smooth muscle cells from spontaneously hypertensive rats

Abstract

An anti-inflammatory cytokine, interleukin-10 (IL-10) exerts inhibitory effects on vascular inflammation. Chemokines promote vascular inflammation and play a pathogenic role in the development and maintenance of hypertension. However, chemokine CCL5 has down-regulatory effects on angiotensin II (Ang II)-induced hypertensive mediators. In the present study, IL-10 increased CCL5 expression and attenuated Ang II-induced CCL5 inhibition significantly in vascular smooth muscle cells (VSMCs) from spontaneously hypertensive rats (SHR), whereas TGF-β had no effect on CCL5 expression or Ang II-induced CCL5 inhibition. Increased CCL5 expression due to IL-10 was mediated mainly through AT2 R activation. Additionally, IL-10 increased activation of AMP-activated protein kinase (AMPK), which further mediated the up-regulatory effect of IL-10 on CCL5 expression. Attenuation of Ang II-induced CCL5 inhibition by IL-10 was associated with suppression of NF-кB activation, and IL-10 inhibited both Ang II-induced IкB-α and IкB-β degradation in SHR VSMCs. Moreover, IL-10 partially mediated the inhibitory effects of CCL5 on Ang II-induced 12-lipoxygenase (LO) and endothelin (ET)-1 expression in SHR VSMCs. Taken together, this study provides novel evidence that IL-10 plays an up-regulatory role in the anti-hypertensive activity of CCL5 in SHR VSMCs.