title: IL-8/CXCL8 Upregulates 12-Lipoxygenase Expression in Vascular Smooth Muscle Cells from Spontaneously Hypertensive Rats.
abstract: BACKGROUND
  We previously demonstrated remarkable differences in the expression of IL-8/CXCL8 in aortic tissues and vascular smooth muscle cells (VSMC) from spontaneously hypertensive rats (SHR) compared to VSMC from normotensive Wistar-Kyoto rats (WKY). In the present study, we investigated the direct effect of IL-8/CXCL8 on expression of 12-lipoxygenase (LO), a hypertensive modulator, in SHR VSMC.
  
  
  METHODS
  Cultured aortic VSMC from SHR and WKY were used. Expression of 12-LO mRNA was determined by real-time polymerase chain reaction. Phosphorlyation of ERK1/2 and production of 12-LO and angiotensin II subtype 1 (AT(1)) receptor were assessed by Western blots. IL-8/CXCL8-stimulated DNA synthesis was determined by measuring incorporation of [(3)H]-thymidine. And effect of IL-8/CXCL8 on vascular tone was determined by phenylephrine-induced contraction of thoracic aortic rings.
  
  
  RESULTS
  Treatment with IL-8/CXCL8 greatly increased 12-LO mRNA expression and protein production compared to treatment with angiotensin II. IL-8/CXCL8 also increased the expression of the AT(1) receptor. The increase in 12-LO induced by IL-8/CXCL8 was inhibited by treatment with an AT(1) receptor antagonist. The induction of 12-LO mRNA production and the proliferation of SHR VSMC by IL-8/CXCL8 was mediated by the ERK pathway. The proliferation of SHR VSMC and the vascular contraction in the thoracic aortic ring, both of which were induced by IL-8/CXCL8, were inhibited by baicalein, a 12-LO inhibitor.
  
  
  CONCLUSIONS
  These results suggest that the potential role of IL-8/CXCL8 in hypertensive processes is likely mediated through the 12-LO pathway.
authors.affiliation: Department of Microbiology, College of Medicine, Yeungnam University, Daegu, Korea.
authors.forename: Jung Hae
authors.initials: JH
authors.lastname: Kim
authors.forename: Young Jin
authors.initials: YJ
authors.lastname: Kang
authors.forename: Hee Sun
authors.initials: HS
authors.lastname: Kim