CCL5 upregulates IL-10 expression and partially mediates the antihypertensive effects of IL-10 in the vascular smooth muscle cells of spontaneously hypertensive rats.

Hypertension research : official journal of the Japanese Society of Hypertension

PubMedID: 25971630

Kim HY, Cha HJ, Kim HS. CCL5 upregulates IL-10 expression and partially mediates the antihypertensive effects of IL-10 in the vascular smooth muscle cells of spontaneously hypertensive rats. Hypertens Res. 2015;.
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.