Upregulation of interleukin-8/CXCL8 in vascular smooth muscle cells from spontaneously hypertensive rats.
Chemokines promote vascular inflammation and play a pathogenic role in the development and maintenance of hypertension. In the present study, the expression of the chemokine interleukin-8/CXCL8 (IL-8/CXCL8) was investigated in cultured vascular smooth muscle cells (VSMC) obtained from the thoracic aorta of spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY). IL-8/CXCL8 expression in thoracic aorta tissue and VSMC in SHR were significantly higher than in WKY. However, the expression of CXCR1 mRNA in VSMC from WKY was higher than that in VSMC from SHR. Angiotensin II (Ang II) induced a higher level of IL-8/CXCL8 mRNA expression in VSMC from SHR than in VSMC from WKY. The time course of Ang II-induced IL-8/CXCL8 expression in VSMC from SHR correlated with those of Ang II-induced CXCL1 and Ang II type 1 (AT1) receptor expression, and the expression of IL-8/CXCL8 by Ang II was inhibited by the AT1 receptor antagonist losartan. The effect of Ang II on IL-8/CXCL8 expression was not dependent on nuclear factor-kappaB (NF-kappaB) activation, but was mediated by an extracellular signal-regulated kinase (ERK) signaling pathway. Although Ang II directly induced IL-8/CXCL8 expression, expression of Ang II-induced IL-8/CXCL8 decreased in VSMC transfected with heme oxygenase-1. These results suggest that IL-8/CXCL8 plays an important role in the pathogenesis of Ang II-induced hypertension and vascular lesions in SHR.
Kim
Hyo Young
HY
Department of Microbiology, College of Medicine, Yeungnam University, Daegu, South Korea.
Kang
Young Jin
YJ
Song
In Hwan
IH
Choi
Hyung Chul
HC
Kim
Hee Sun
HS
D000804:Angiotensin II / Q000494:pharmacology; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology; D000818:Animals; D002478:Cells, Cultured; D004195:Disease Models, Animal; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D051547:Heme Oxygenase-1 / Q000235:genetics / Q000378:metabolism; D006973:Hypertension / Q000378:metabolism* / Q000473:pathology; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism*; D019808:Losartan / Q000494:pharmacology; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000378:metabolism* / Q000473:pathology; D016328:NF-kappa B / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D015398:Signal Transduction / Q000502:physiology; D014162:Transfection; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology*; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D047228:Angiotensin II Type 1 Receptor Blockers; D016209:Interleukin-8; D016328:NF-kappa B; D012333:RNA, Messenger; D014662:Vasoconstrictor Agents; D000804:Angiotensin II; D051547:Heme Oxygenase-1; D048049:Extracellular Signal-Regulated MAP Kinases; D019808:Losartan