title: CCL5 upregulates IL-10 expression and partially mediates the antihypertensive effects of IL-10 in the vascular smooth muscle cells of spontaneously hypertensive rats.
abstract: Interleukin (IL)-10 inhibits angiotensin (Ang) II-induced vascular dysfunction and reduces blood pressure in hypertensive pregnant rats. The chemokine CCL5 has also been shown to downregulate Ang II-induced hypertensive mediators in spontaneously hypertensive rats (SHRs). This study investigated the effects of CCL5 on IL-10 expression, as well as its mechanisms of action in the vascular smooth muscle cells (VSMCs) of SHRs. CCL5 increased IL-10 expression in the VSMCs of SHRs; the s.c. injection of CCL5 (1.5 μg kg(-1), twice a day) for 3 weeks into SHRs with established hypertension upregulated IL-10 expression in both the thoracic aorta and the VSMCs and decreased systolic blood pressure. CCL5-induced the elevation of IL-10 expression, an effect mediated primarily via the activation of an Ang II subtype II receptor (AT2 R). Dimethylarginine dimethylaminohydrolase (DDAH)-1 activity also contributed to the elevation of IL-10 expression via CCL5 in the VSMCs of SHRs. Moreover, CCL5 partially mediated the inhibitory effects of IL-10 on Ang II-induced 12-lipoxygenase (LO) and endothelin (ET)-1 expression in the VSMCs of SHRs. Taken together, this study provides novel evidence that CCL5 plays a role in the upregulation of IL-10 activity in the VSMCs of SHRs.
authors.affiliation: Department of Microbiology, College of Medicine, Yeungnam University, Daegu, South Korea.
authors.forename: Hye Young
authors.initials: HY
authors.lastname: Kim
authors.affiliation: Department of Microbiology, College of Medicine, Yeungnam University, Daegu, South Korea.
authors.forename: Hye Ju
authors.initials: HJ
authors.lastname: Cha
authors.affiliation: Department of Microbiology, College of Medicine, Yeungnam University, Daegu, South Korea.
authors.forename: Hee Sun
authors.initials: HS
authors.lastname: Kim
mesh_terms: D000581:Amidohydrolases / Q000378:metabolism; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001013:Aorta, Thoracic / Q000187:drug effects / Q000378:metabolism; D001092:Arachidonate 12-Lipoxygenase / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D018946:Chemokine CCL5 / Q000494:pharmacology*; D019332:Endothelin-1 / Q000096:biosynthesis; D016753:Interleukin-10 / Q000096:biosynthesis* / Q000494:pharmacology*; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D032389:Myocytes, Smooth Muscle / Q000187:drug effects*; D034741:RNA, Small Interfering / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY
chemical_list: D000959:Antihypertensive Agents; D018946:Chemokine CCL5; D019332:Endothelin-1; C108335:RANTES, Met-; D034741:RNA, Small Interfering; D016753:Interleukin-10; D001092:Arachidonate 12-Lipoxygenase; D000581:Amidohydrolases; C059999:dimethylargininase