title: 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.
authors.affiliation: Department of Microbiology, College of Medicine, Yeungnam University, 317-1 Daemyungdong, Namgu, Daegu 705-717, Republic of Korea.
authors.forename: Hye Young
authors.initials: HY
authors.lastname: Kim
authors.affiliation: Department of Microbiology, College of Medicine, Yeungnam University, 317-1 Daemyungdong, Namgu, Daegu 705-717, Republic of Korea. Electronic address: heesun@med.yu.ac.kr.
authors.forename: Hee Sun
authors.initials: HS
authors.lastname: Kim
mesh_terms: D000263:Adenylate Kinase / Q000378:metabolism; D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D002478:Cells, Cultured; D018946:Chemokine CCL5 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D024202:Electrophoretic Mobility Shift Assay; D016753:Interleukin-10 / Q000502:physiology*; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000201:enzymology / Q000378:metabolism; D034741:RNA, Small Interfering; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D060888:Real-Time Polymerase Chain Reaction; D015854:Up-Regulation / Q000502:physiology*
chemical_list: D018946:Chemokine CCL5; D034741:RNA, Small Interfering; D000804:Angiotensin II; D016753:Interleukin-10; D000263:Adenylate Kinase
keywords: Angiotensin II; CCL5; Hypertension; Interleukin-10; Vascular smooth muscle cells (VSMCs)