고혈압 쥐와 정상혈압 쥐의 혈관 평활근 세포에서 케모카인 발현 비교

Abstract

Background：The action of chemokines to the vascular inflammation plays a pathogenic role in the development and maintenance of hypertension. Materials and methods：In the present study, the expression of chemokine IL-8/CXCL8, MCP-1/CCL2 and RANTES/CCL5 was investigated in cultured vascular smooth muscle cells (VSMC) obtained from the thoracic aorta of normotensive Wister-Kyoto rat (WKY) and spontaneously hypertensive rat (SHR). We used real-time PCR and western blotting. Result：The expressions of IL-8/CXCL8, and MCP-1/CCL2 mRNA were stronger in VSMC from SHR than in WKY. However, the expression of RANTES/CCL5 was stronger in VSMC from WKY than in SHR. Expressions of CXCR1, CCR2, CD14 and PPARγ mRNA were stronger in VSMC from WKY than in SHR. Expressions of LPS-induced IL-8/CXCL8 and MCP-1/CCL2 mRNA were stronger in VSMC from SHR, but expression of LPS-induced RANTES/CCL5 was stronger in VSMC from WKY. A PPAR-γ ligand, 15-deoxy-Δ12, 14- prostaglandin J2 (15d-PGJ2) which possesses anti-inflammatory activity suppressed the expressions of LPS-induced IL-8/CXCL8, MCP-1/CCL2 and RANTES/CCL5 in VSMC from WKY and the expressions of LPS-induced MCP-1/CCL2 and RANTES/CCL5 expressions in SHR. But, the expression of LPS-induced IL-8/CXCL8 mRNA in SHR was increased by 15d- PGJ2. Angiotensin II (AngII) also induced IL-8/CXCL8 and MCP-1/CCL2 mRNA expressions in VSMC from SHR, but inhibited the expression of RANTES/CCL5 mRNA. Activities of LPS, or AngII-induced MAP kinases were stronger in VSMC from SHR than in WKY. Expression of AngII-induced IL-8/CXCL8 mRNA was associated with ERK phathway, and the expression of AngII-induced MCP-1/CCL2 mRNA was associated with p38 pathway, and the inhibition of RANTES/CCL5 mRNA by AngII was not associated with MAP Kinases pathways. Conclusion：Chemokine IL-8/CXCL8 and MCP-1/CCL2, not RANTES/CCL5, has a possibility to play a critical role in the pathogenesis of hypertension in the SHR.